document_title: Neurotransmitter

question_text: which category of drugs includes many substances that are chemically similar to neurotransmitters

text: Neurotransmitter

text: Mechanism[edit]

text: Neurotransmitters are stored in a synapse in synaptic vesicles, clustered beneath the membrane in the axon terminal located at the presynaptic side of the synapse. Neurotransmitters are released into and diffused across the synaptic cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse.[3]

text: Most neurotransmitters are about the size of a single amino acid, however, some neurotransmitters may be the size of larger proteins or peptides. A released neurotransmitter is typically available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission.

text: In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level "baseline" release also occurs without electrical stimulation. The released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way. This neuron may be connected to many more neurons, and if the total of excitatory influences are greater than those of inhibitory influences, the neuron will also "fire". Ultimately it will create a new action potential at its axon hillock to release neurotransmitters and pass on the information to yet another neighboring neuron.[4]

text: Discovery[edit]

text: Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal (1852–1934), a 20 to 40 nm gap between neurons, known today as the synaptic cleft, was discovered. The presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, and in 1921 German pharmacologist Otto Loewi (1873–1961) confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine (ACh)—the first known neurotransmitter.[5] Some neurons do, however, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another.[6]

text: Identification[edit]

text: There are four main criteria for identifying neurotransmitters:

text:
The chemical must be synthesized in the neuron or otherwise be present in it.
When the neuron is active, the chemical must be released and produce a response in some target.
The same response must be obtained when the chemical is experimentally placed on the target.
A mechanism must exist for removing the chemical from its site of activation after its work is done.

tag: ol

text: However, given advances in pharmacology, genetics, and chemical neuroanatomy, the term "neurotransmitter" can be applied to chemicals that:

text:
Carry messages between neurons via influence on the postsynaptic membrane.
Have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse.
Communicate by sending reverse-direction messages that affect the release or reuptake of transmitters.

text: The anatomical localization of neurotransmitters is typically determined using immunocytochemical techniques, which identify the location of either the transmitter substances themselves, or of the enzymes that are involved in their synthesis. Immunocytochemical techniques have also revealed that many transmitters, particularly the neuropeptides, are co-localized, that is, one neuron may release more than one transmitter from its synaptic terminal.[7] Various techniques and experiments such as staining, stimulating, and collecting can be used to identify neurotransmitters throughout the central nervous system.[8]

text: Types[edit]

text: There are many different ways to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.

text: Major neurotransmitters:

text:
Amino acids: glutamate,[4] aspartate, D-serine, γ-aminobutyric acid (GABA), glycine
Gasotransmitters: nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S)
Monoamines: dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SER, 5-HT)
Trace amines: phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronamine, octopamine, tryptamine, etc.
Peptides: somatostatin, substance P, cocaine and amphetamine regulated transcript, opioid peptides[9]
Purines: adenosine triphosphate (ATP), adenosine
Others: acetylcholine (ACh), anandamide, etc.

text: In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are "co-released" along with a small-molecule transmitter. Nevertheless, in some cases a peptide is the primary transmitter at a synapse. β-endorphin is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with opioid receptors in the central nervous system.

text: Single ions (such as synaptically released zinc) are also considered neurotransmitters by some,[10] as well as some gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S).[11] The gases are produced in the neural cytoplasm and are immediately diffused through the cell membrane into the extracellular fluid and into nearby cells to stimulate production of second messengers. Soluble gas neurotransmitters are difficult to study, as they act rapidly and are immediately broken down, existing for only a few seconds.

text: The most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human brain.[4] The next most prevalent is Gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine levels.

text: List of neurotransmitters, peptides, and gasotransmitters[edit]

text:
Category
Name
Abbreviation
Metabotropic
Ionotropic

Small: Amino acids (Arg)
Arginine

α2-Adrenergic receptors, imidazoline receptors
NMDA receptors

Small: Amino acids
Asparagine
Asp
–
NMDA receptors

Small: Amino acids
Glutamate
Glu
Metabotropic glutamate receptors
NMDA receptors, kainate receptors, AMPARs

Small: Amino acids
Gamma-aminobutyric acid
GABA
GABAB receptors
GABAA receptors, GABAA-ρ receptors

Small: Amino acids
Glycine
Gly
–
NMDA receptors, glycine receptors

Small: Amino acids
D-serine
Ser
–
NMDA receptors

Small: Acetylcholine
Acetylcholine
Ach
Muscarinic acetylcholine receptors
Nicotinic acetylcholine receptors

Small: Monoamine (Phe/Tyr)
Dopamine
DA
Dopamine receptors, trace amine-associated receptor 1[12][13]
–

Small: Monoamine (Phe/Tyr)
Norepinephrine (noradrenaline)
NE, NAd
Adrenergic receptors
–

Small: Monoamine (Phe/Tyr)
Epinephrine (adrenaline)
Epi, Ad
Adrenergic receptors
–

Small: Monoamine (Trp)
Serotonin (5-hydroxytryptamine)
5-HT
Serotonin receptors (all except 5-HT3)
5-HT3

Small: Monoamine (His)
Histamine
H
Histamine receptors
–

Small: Trace amine (Phe)
Phenethylamine
PEA
Human trace amine-associated receptors: hTAAR1, hTAAR2
–

Small: Trace amine (Phe)
N-methylphenethylamine
NMPEA
hTAAR1
–

Small: Trace amine (Phe/Tyr)
Tyramine
TYR
hTAAR1, hTAAR2
–

Small: Trace amine (Phe/Tyr)
Octopamine
Oct
hTAAR1
–

Small: Trace amine (Phe/Tyr)
Synephrine
Syn
hTAAR1
–

Small: Trace amine (Trp)
Tryptamine

hTAAR1, various serotonin receptors
–

Small: Trace amine (Trp)
N-methyltryptamine
NMT
hTAAR1, various serotonin receptors
–

Lipid
Anandamide
AEA
Cannabinoid receptors
–

Lipid
2-Arachidonoylglycerol
2-AG
Cannabinoid receptors
–

Lipid
2-Arachidonyl glyceryl ether
2-AGE
Cannabinoid receptors
–

Lipid
N-Arachidonoyl dopamine
NADA
Cannabinoid receptors
TRPV1

Lipid
Virodhamine

Cannabinoid receptors
–

Small: Purine
Adenosine
Ado
Adenosine receptors
–

Small: Purine
Adenosine triphosphate
ATP
P2Y receptors
P2X receptors

PP: Galanins
Galanin

GALR1, GALR2, GALR3
–

PP: Galanins
Galanin-like peptide

GALR1, GALR2, GALR3
–

PP: Gastrins
Gastrin

Cholecystokinin B receptor
–

PP: Gastrins
Cholecystokinin
CCK
Cholecystokinin receptors
–

PP: Neurohypophyseals
Vasopressin
AVP
Vasopressin receptors
–

PP: Neurohypophyseals
Oxytocin
OT
Oxytocin receptor
–

PP: Neurohypophyseals
Neurophysin I

–
–

PP: Neurohypophyseals
Neurophysin II

–
–

PP: Neuropeptide B/W
Neuropeptide B
NPB
NPBW1, NPBW2
–

PP: Neuropeptide B/W
Neuropeptide S
NPS
Neuropeptide S receptors
–

PP: Neuropeptide Y
Neuropeptide Y
NY
Neuropeptide Y receptors
–

PP: Neuropeptide Y
Pancreatic polypeptide
PP
–
–

PP: Neuropeptide Y
Peptide YY
PYY
–
–

PP: Opioids
Enkephalin

δ-Opioid receptor
–

PP: Opioids
Dynorphin

κ-Opioid receptor
–

PP: Opioids
Endorphin

μ-Opioid receptors
–

PP: Opioids
Endomorphin

μ-Opioid receptors
–

PP: Orexins
Orexin A
OX-A
Orexin receptors
–

PP: Orexins
Orexin B
OX-B
Orexin receptors
–

PP: Secretins
Secretin

Secretin receptor
–

PP: Secretins
Motilin

Motilin receptor
–

PP: Secretins
Glucagon

Glucagon receptor
–

PP: Secretins
Vasoactive intestinal peptide
VIP
Vasoactive intestinal peptide receptors
–

PP: Secretins
Growth hormone–releasing hormone
GHRH
Growth hormone–releasing hormone receptor
–

PP: Somatostatins
Somatostatin

Somatostatin receptors
–

PP: Tachykinins
Neurokinin A

–
–

PP: Tachykinins
Neurokinin B

–
–

PP: Tachykinins
Substance P

–
–

PP: Tachykinins
Neuropeptide K

–
–

PP: Other
Adrenocorticotropic hormone
ACTH
ACTH receptor
–

PP: Other
N-Acetylaspartylglutamate
NAAG
Metabotropic glutamate receptor 3 (mGluR3)
–

PP: Other
Cocaine- and amphetamine-regulated transcript
CART
Unknown Gi/Go-coupled receptor[14]
–

PP: Other
Bombesin

–
–

PP: Other
Gastrin releasing peptide
GRP
–
–

PP: Other
Kisspeptin

GPR54
–

Gasotransmitter
Nitric oxide
NO
Soluble guanylyl cyclase
–

Gasotransmitter
Carbon monoxide
CO
–
Heme bound to potassium channels

Gasotransmitter
Hydrogen sulfide
H2S
–
–

text: Actions[edit]

text: Neurons form elaborate networks through which nerve impulses—action potentials—travel. Each neuron has as many as 15,000 connections with neighboring neurons.

text: Neurons do not touch each other (except in the case of an electrical synapse through a gap junction); instead, neurons interact at contact points called synapses: a junction within two nerve cells, consisting of a miniature gap within which impulses are carried by a neurotransmitter. A neuron transports its information by way of a nerve impulse called an action potential. When an action potential arrives at the synapse's presynaptic terminal button, it may stimulate the release of neurotransmitters. These neurotransmitters are released into the synaptic cleft to bind onto the receptors of the postsynaptic membrane and influence another cell, either in an inhibitory or excitatory way. The next neuron may be connected to many more neurons, and if the total of excitatory influences minus inhibitory influences is great enough, it will also "fire". That is to say, it will create a new action potential at its axon hillock, releasing neurotransmitters and passing on the information to yet another neighboring neuron.

text: Excitatory and inhibitory[edit]

text: A neurotransmitter can influence the function of a neuron through a remarkable number of mechanisms. In its direct actions in influencing a neuron’s electrical excitability, however, a neurotransmitter acts in only one of two ways: excitatory or inhibitory. A neurotransmitter influences trans-membrane ion flow either to increase (excitatory) or to decrease (inhibitory) the probability that the cell with which it comes in contact will produce an action potential. Thus, despite the wide variety of synapses, they all convey messages of only these two types, and they are labeled as such. Type I synapses are excitatory in their actions, whereas type II synapses are inhibitory. Each type has a different appearance and is located on different parts of the neurons under its influence. Each neuron receives thousands of excitatory and inhibitory signals every second.[citation needed]

text: Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas type II (inhibitory) synapses are typically located on a cell body. In addition, Type I synapses have round synaptic vesicles, whereas the vesicles of type II synapses are flattened. The material on the presynaptic and post-synaptic membranes is denser in a Type I synapse than it is in a type II, and the type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Type II synapse.

text: The different locations of type I and type II synapses divide a neuron into two zones: an excitatory dendritic tree and an inhibitory cell body. From an inhibitory perspective, excitation comes in over the dendrites and spreads to the axon hillock to trigger an action potential. If the message is to be stopped, it is best stopped by applying inhibition on the cell body, close to the axon hillock where the action potential originates. Another way to conceptualize excitatory–inhibitory interaction is to picture excitation overcoming inhibition. If the cell body is normally in an inhibited state, the only way to generate an action potential at the axon hillock is to reduce the cell body’s inhibition. In this "open the gates" strategy, the excitatory message is like a racehorse ready to run down the track, but first the inhibitory starting gate must be removed.[15]

text: Examples of important neurotransmitter actions[edit]

text: As explained above, the only direct action of a neurotransmitter is to activate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors that the transmitter binds to.

text: Here are a few examples of important neurotransmitter actions:

text:
Glutamate is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can overstimulate the brain and lead to excitotoxicity causing cell death resulting in seizures or strokes.[16] Excitotoxicity has been implicated in certain chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington disease, and Parkinson's disease.[17]
GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA.[18] Correspondingly, glycine is the inhibitory transmitter in the spinal cord.
Acetylcholine was the first neurotransmitter discovered in the peripheral and central nervous systems. It activates skeletal muscles in the somatic nervous system and may either excite or inhibit internal organs in the autonomic system.[8] It is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poison curare acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain, but using different types of receptors, including nicotinic and muscarinic receptors.[19]
Dopamine has a number of important functions in the brain; this includes regulation of motor behavior, pleasures related to motivation and also emotional arousal. It plays a critical role in the reward system; Parkinson's disease has been linked to low levels of dopamine and schizophrenia has been linked to high levels of dopamine.[20]
Serotonin is a monoamine neurotransmitter. Most is produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine system. It is speculated to have a role in depression, as some depressed patients are seen to have lower concentrations of metabolites of serotonin in their cerebrospinal fluid and brain tissue.[21]
Norepinephrine which focuses on the central nervous system, based on sleep patterns, focus and alertness. It is synthesized from tyrosine.
Epinephrine which is also synthesized from tyrosine takes part in controlling the adrenal glands. It plays a role in sleep, with ones ability to become and stay alert, and the fight-or-flight response.
Histamine works with the central nervous system (CNS), specifically the hypothalamus (tuberomammillary nucleus) and CNS mast cells.

text: Brain neurotransmitter systems[edit]

text: Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large volumes of the brain, called volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system, and the cholinergic system, among others. Trace amines have a modulatory effect on neurotransmission in monoamine pathways (i.e., dopamine, norepinephrine, and serotonin pathways) throughout the brain via signaling through trace amine-associated receptor 1.[22][23] A brief comparison of these systems follows:

text:
Neurotransmitter systems in the brain

System
Pathway origin and projections
Regulated cognitive processes and behaviors

Noradrenaline system
[24][25][26][27][28][29]
Noradrenergic pathways:

Locus coeruleus (LC) projections

LC → Amygdala and Hippocampus
LC → Brain stem and Spinal cord
LC → Cerebellum
LC → Cerebral cortex
LC → Hypothalamus
LC → Tectum
LC → Thalamus
LC → Ventral tegmental area

Lateral tegmental field (LTF) projections

LTF → Brain stem and Spinal cord
LTF → Olfactory bulb

anxiety
arousal (wakefulness)
circadian rhythm
cognitive control and working memory (co-regulated by dopamine)
feeding and energy homeostasis
medullary control of respiration
negative emotional memory
nociception (perception of pain)
reward (minor role)

Dopamine system
[26][27][28][30][31][32]
Dopaminergic pathways:

Ventral tegmental area (VTA) projections

VTA → Amygdala
VTA → Cingulate cortex
VTA → Hippocampus
VTA → Ventral striatum (Mesolimbic pathway)
VTA → Olfactory bulb
VTA → Prefrontal cortex (Mesocortical pathway)

Nigrostriatal pathway

Substantia nigra pars compacta → Dorsal striatum

Tuberoinfundibular pathway

Arcuate nucleus → Median eminence

arousal (wakefulness)
aversion
cognitive control and working memory (co-regulated by norepinephrine)
emotion and mood
motivation (motivational salience)
motor function
positive reinforcement
reward (primary mediator)
sexual arousal, orgasm, and refractory period (via neuroendocrine regulation)

Histamine system
[27][28][33]
Histaminergic pathways:

Tuberomammillary nucleus (TMN) projections

TMN → Cerebral cortex
TMN → Hippocampus
TMN → Neostriatum
TMN → Nucleus accumbens
TMN → Amygdala
TMN → Hypothalamus

arousal (wakefulness)
feeding and energy homeostasis
learning
memory

Serotonin system
[24][26][27][28][34][35][36]
Serotonergic pathways:
Caudal nuclei (CN):
Raphe magnus, raphe pallidus, and raphe obscurus

Caudal projections

CN → Cerebral cortex
CN → Thalamus
CN → Caudate-putamen and nucleus accumbens
CN → Substantia nigra and ventral tegmental area

Rostral nuclei (RN):
Nucleus linearis, dorsal raphe, medial raphe, and raphe pontis

Rostral projections

RN → Amygdala
RN → Cingulate cortex
RN → Hippocampus
RN → Hypothalamus
RN → Neocortex
RN → Septum
RN → Thalamus
RN → Ventral tegmental area

arousal (wakefulness)
body temperature regulation
emotion and mood, potentially including aggression
feeding and energy homeostasis
reward (minor role)
sensory perception

Acetylcholine system
[24][26][27][28][37]
Cholinergic pathways:
Forebrain cholinergic nuclei (FCN):
Nucleus basalis of Meynert, medial septal nucleus, and diagonal band

Forebrain nuclei projections

FCN → Hippocampus
FCN → Cerebral cortex
FCN → Limbic cortex and sensory cortex

Brainstem cholinergic nuclei (BCN):
Pedunculopontine nucleus, laterodorsal tegmentum, medial habenula, and
parabigeminal nucleus

Brainstem nuclei projections

BCN → Ventral tegmental area
BCN → Thalamus

arousal (wakefulness)
emotion and mood
learning
motor function
motivation (motivational salience)
short-term memory
reward (minor role)

text: Drug effects[edit]

text: Understanding the effects of drugs on neurotransmitters comprises a significant portion of research initiatives in the field of neuroscience. Most neuroscientists involved in this field of research believe that such efforts may further advance our understanding of the circuits responsible for various neurological diseases and disorders, as well as ways to effectively treat and someday possibly prevent or cure such illnesses.[38][medical citation needed]

text: Drugs can influence behavior by altering neurotransmitter activity. For instance, drugs can decrease the rate of synthesis of neurotransmitters by affecting the synthetic enzyme(s) for that neurotransmitter. When neurotransmitter syntheses are blocked, the amount of neurotransmitters available for release becomes substantially lower, resulting in a decrease in neurotransmitter activity. Some drugs block or stimulate the release of specific neurotransmitters. Alternatively, drugs can prevent neurotransmitter storage in synaptic vesicles by causing the synaptic vesicle membranes to leak. Drugs that prevent a neurotransmitter from binding to its receptor are called receptor antagonists. For example, drugs used to treat patients with schizophrenia such as haloperidol, chlorpromazine, and clozapine are antagonists at receptors in the brain for dopamine. Other drugs act by binding to a receptor and mimicking the normal neurotransmitter. Such drugs are called receptor agonists. An example of a receptor agonist is Valium, a benzodiazepine that mimics effects of the endogenous neurotransmitter gamma-aminobutyric acid (GABA) to decrease anxiety. Other drugs interfere with the deactivation of a neurotransmitter after it has been released, thereby prolonging the action of a neurotransmitter. This can be accomplished by blocking re-uptake or inhibiting degradative enzymes. Lastly, drugs can also prevent an action potential from occurring, blocking neuronal activity throughout the central and peripheral nervous system. Drugs such as tetrodotoxin that block neural activity are typically lethal.

text: Drugs targeting the neurotransmitter of major systems affect the whole system, which can explain the complexity of action of some drugs. Cocaine, for example, blocks the re-uptake of dopamine back into the presynaptic neuron, leaving the neurotransmitter molecules in the synaptic gap for an extended period of time. Since the dopamine remains in the synapse longer, the neurotransmitter continues to bind to the receptors on the postsynaptic neuron, eliciting a pleasurable emotional response. Physical addiction to cocaine may result from prolonged exposure to excess dopamine in the synapses, which leads to the downregulation of some post-synaptic receptors. After the effects of the drug wear off, an individual can become depressed due to decreased probability of the neurotransmitter binding to a receptor. Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI), which blocks re-uptake of serotonin by the presynaptic cell which increases the amount of serotonin present at the synapse and furthermore allows it to remain there longer, providing potential for the effect of naturally released serotonin.[39] AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

text: Agonists[edit]

text: This section needs expansion with: coverage of full agonists and their distinction from partial agonist and inverse agonist.. You can help by adding to it. (August 2015)

text: An agonist is a chemical capable of binding to a receptor, such as a neurotransmitter receptor, and initiating the same reaction typically produced by the binding of the endogenous substance.[40] An agonist of a neurotransmitter will thus initiate the same receptor response as the transmitter. In neurons, an agonist drug may activate neurotransmitter receptors either directly or indirectly. Direct-binding agonists can be further characterized as full agonists, partial agonists, inverse agonists.[citation needed]

text: Direct agonists act similar to a neurotransmitter by binding directly to its associated receptor site(s), which may be located on the presynaptic neuron or postsynaptic neuron, or both.[41] Typically, neurotransmitter receptors are located on the postsynaptic neuron, while neurotransmitter autoreceptors are located on the presynaptic neuron, as is the case for monoamine neurotransmitters;[22] in some cases, a neurotransmitter utilizes retrograde neurotransmission, a type of feedback signaling in neurons where the neurotransmitter is released postsynaptically and binds to target receptors located on the presynaptic neuron.[42][note 1] Nicotine, a compound found in tobacco, is a direct agonist of most nicotinic acetylcholine receptors, mainly located in cholinergic neurons.[43] Opiates, such as morphine, heroin, hydrocodone, oxycodone, codeine, and methadone, are μ-opioid receptor agonists; this action mediates their euphoriant and pain relieving properties.[43]

text: Indirect agonists increase the binding of neurotransmitters at their target receptors by stimulating the release or preventing the reuptake of neurotransmitters.[41] Some indirect agonists trigger neurotransmitter release and prevent neurotransmitter reuptake. Amphetamine, for example, is an indirect agonist of postsynaptic dopamine, norepinephrine, and serotonin receptors in each their respective neurons;[22][23] it produces both neurotransmitter release into the presynaptic neuron and subsequently the synaptic cleft and prevents their reuptake from the synaptic cleft by activating TAAR1, a presynaptic G protein-coupled receptor, and binding to a site on VMAT2, a type of monoamine transporter located on synaptic vesicles within monoamine neurons.[22][23]

text: Antagonists[edit]

text: An antagonist is a chemical that acts within the body to reduce the physiological activity of another chemical substance (as an opiate); especially one that opposes the action on the nervous system of a drug or a substance occurring naturally in the body by combining with and blocking its nervous receptor.[44]

text: There are two main types of antagonist: direct-acting Antagonist and indirect-acting Antagonists:

text:
Direct-acting antagonist- which takes up space present on receptors which are otherwise taken up by neurotransmitters themselves. This results in neurotransmitters being blocked from binding to the receptors. The most common is called Atropine.
Indirect-acting antagonist- drugs that inhibit the release/production of neurotransmitters (e.g., Reserpine).

text: Drug antagonists[edit]

text: An antagonist drug is one that attaches (or binds) to a site called a receptor without activating that receptor to produce a biological response. It is therefore said to have no intrinsic activity. An antagonist may also be called a receptor "blocker" because they block the effect of an agonist at the site. The pharmacological effects of an antagonist therefore result in preventing the corresponding receptor site's agonists (e.g., drugs, hormones, neurotransmitters) from binding to and activating it. Antagonists may be "competitive" or "irreversible".

text: A competitive antagonist competes with an agonist for binding to the receptor. As the concentration of antagonist increases, the binding of the agonist is progressively inhibited, resulting in a decrease in the physiological response. High concentration of an antagonist can completely inhibit the response. This inhibition can be reversed, however, by an increase of the concentration of the agonist, since the agonist and antagonist compete for binding to the receptor. Competitive antagonists, therefore, can be characterized as shifting the dose-response relationship for the agonist to the right. In the presence of a competitive antagonist, it takes an increased concentration of the agonist to produce the same response observed in the absence of the antagonist.

text: An irreversible antagonist binds so strongly to the receptor as to render the receptor unavailable for binding to the agonist. Irreversible antagonists may even form covalent chemical bonds with the receptor. In either case, if the concentration of the irreversible antagonist is high enough, the number of unbound receptors remaining for agonist binding may be so low that even high concentrations of the agonist do not produce the maximum biological response.[45]

text: Precursors[edit]

text:
Biosynthetic pathways for catecholamines and trace amines in the human brain[46][47][48]

L-Phenylalanine
L-Tyrosine
L-DOPA
Epinephrine
Phenethylamine
p-Tyramine
Dopamine
Norepinephrine
N-Methylphenethylamine
N-Methyltyramine
p-Octopamine
Synephrine
3-Methoxytyramine
AADC
AADC
AADC
primary
pathway
PNMT
PNMT
PNMT
PNMT
AAAH
AAAH
brain
CYP2D6
minor
pathway
COMT
DBH
DBH

In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

text: While intake of neurotransmitter precursors does increase neurotransmitter synthesis, evidence is mixed as to whether neurotransmitter release and postsynaptic receptor firing is increased. Even with increased neurotransmitter release, it is unclear whether this will result in a long-term increase in neurotransmitter signal strength, since the nervous system can adapt to changes such as increased neurotransmitter synthesis and may therefore maintain constant firing.[49][unreliable medical source?] Some neurotransmitters may have a role in depression and there is some evidence to suggest that intake of precursors of these neurotransmitters may be useful in the treatment of mild and moderate depression.[49][unreliable medical source?][50]

text: Catecholamine and trace amine precursors[edit]

text: L-DOPA, a precursor of dopamine that crosses the blood–brain barrier, is used in the treatment of Parkinson's disease. For depressed patients where low activity of the neurotransmitter norepinephrine is implicated, there is only little evidence for benefit of neurotransmitter precursor administration. L-phenylalanine and L-tyrosine are both precursors for dopamine, norepinephrine, and epinephrine. These conversions require vitamin B6, vitamin C, and S-adenosylmethionine. A few studies suggest potential antidepressant effects of L-phenylalanine and L-tyrosine, but there is much room for further research in this area.[49][unreliable medical source?]

text: Serotonin precursors[edit]

text: Administration of L-tryptophan, a precursor for serotonin, is seen to double the production of serotonin in the brain. It is significantly more effective than a placebo in the treatment of mild and moderate depression.[49][unreliable medical source?] This conversion requires vitamin C.[21] 5-hydroxytryptophan (5-HTP), also a precursor for serotonin, is more effective than a placebo.[49][unreliable medical source?]

text: Diseases and disorders[edit]

text: Diseases and disorders may also affect specific neurotransmitter systems. For example, problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to move as they want to, resulting in stiffness, tremors or shaking, and other symptoms. Some studies suggest that having too little or too much dopamine or problems using dopamine in the thinking and feeling regions of the brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD). Similarly, after some research suggested that drugs that block the recycling, or reuptake, of serotonin seemed to help some people diagnosed with depression, it was theorized that people with depression might have lower-than-normal serotonin levels. Though widely popularized, this theory was not borne out in subsequent research.[51] Furthermore, problems with producing or using glutamate have been suggestively and tentatively linked to many mental disorders, including autism, obsessive compulsive disorder (OCD), schizophrenia, and depression.[52]

text: Neurotransmitter imbalance[edit]

text: Generally, there are no scientifically established "norms" for appropriate levels or "balances" of different neurotransmitters. It is in most cases pragmatically impossible to even measure levels of neurotransmitters in a brain or body at any distinct moments in time. Neurotransmitters regulate each other's release, and weak consistent imbalances in this mutual regulation were linked to temperament in healthy people .[53][54][55][56][57] Strong imbalances or disruptions to neurotransmitter systems have been associated with many diseases and mental disorders. These include Parkinson's, depression, insomnia, Attention Deficit Hyperactivity Disorder (ADHD), anxiety, memory loss, dramatic changes in weight and addictions. Chronic physical or emotional stress can be a contributor to neurotransmitter system changes. Genetics also plays a role in neurotransmitter activities. Apart from recreational use, medications that directly and indirectly interact one or more transmitter or its receptor are commonly prescribed for psychiatric and psychological issues. Notably, drugs interacting with serotonin and norepinephrine are prescribed to patients with problems such as depression and anxiety—though the notion that there is much solid medical evidence to support such interventions has been widely criticized.[58]

text: Elimination of neurotransmitters[edit]

text: A neurotransmitter must be broken down once it reaches the post-synaptic cell to prevent further excitatory or inhibitory signal transduction. This allows new signals to be produced from the adjacent nerve cells. When the neurotransmitter has been secreted into the synaptic cleft, it binds to specific receptors on the postsynaptic cell, thereby generating a postsynaptic electrical signal. The transmitter must then be removed rapidly to enable the postsynaptic cell to engage in another cycle of neurotransmitter release, binding, and signal generation. Neurotransmitters are terminated in three different ways:

text:
Diffusion – the neurotransmitter detaches from receptor, drifting out of the synaptic cleft, here it becomes absorbed by glial cells.
Enzyme degradation – special chemicals called enzymes break it down.
Reuptake – re-absorption of a neurotransmitter into the neuron. Transporters, or membrane transport proteins, pump neurotransmitters from the synaptic cleft back into axon terminals (the presynaptic neuron) where they are stored.[59]

text: For example, choline is taken up and recycled by the pre-synaptic neuron to synthesize more ACh. Other neurotransmitters such as dopamine are able to diffuse away from their targeted synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at regulatory points, which may be targeted by the body's regulatory system or by recreational drugs.


document_title: List of VFL/AFL premiers

question_text: who has won the most afl grand finals in a row

root

text: List of VFL/AFL premiers

text: List of premiers[edit]

text: The following is a list of the premiers, and the grand final results and circumstances. Most conventional grand finals are a single match at the end of a finals series where the winner of the match wins the premiership.

tag: p

text: Under the early VFL finals systems in 1898-1923 and 1925-1930, the circumstances of the grand final were often different: in twenty-nine of these thirty-two years, the minor premiers had the right to challenge the winner of the finals series for the premiership, meaning the grand finals of this era were a mixture of challenge matches, non-challenge matches (which would have been followed by challenge matches had the minor premier been defeated), while in 1901, 1903 and 1906 there was no right of challenge. Regardless of the circumstances at that time, all of these games are now recognised as grand finals.

text: VFL/AFL premierships[edit]

text:
Season

Premiers

Runners-up

Score

Venue

Attendance

Date

Victorian Football League founded

1897
Essendon
Geelong
N/A
N/A
N/A
N/A

1898
Fitzroy
Essendon
5.8 (38) d. 3.5 (23)
Junction Oval
16,538
24 September 1898

1899
Fitzroy (2)
South Melbourne
3.9 (27) d. 3.8 (26)
Junction Oval
4,823
16 September 1899

1900
Melbourne
Fitzroy
4.10 (34) d. 3.12 (30)
East Melbourne Cricket Ground
20,181
22 September 1900

1901
Essendon (2)
Collingwood
6.7 (43) d. 2.4 (16)
Lake Oval
30,031
7 September 1901

1902
Collingwood
Essendon (2)
9.6 (60) d. 3.9 (27)
Melbourne Cricket Ground
35,202
20 September 1902

1903
Collingwood (2)
Fitzroy (2)
4.7 (31) d. 3.11 (29)
Melbourne Cricket Ground
32,263
12 September 1903

1904
Fitzroy (3)
Carlton
9.7 (61) d. 5.7 (37)
Melbourne Cricket Ground
32,688
17 September 1904

1905
Fitzroy (4)
Collingwood (2)
4.6 (30) d. 2.5 (17)
Melbourne Cricket Ground
30,000
30 September 1905

1906
Carlton
Fitzroy (3)
15.4 (94) d. 6.9 (45)
Melbourne Cricket Ground
44,437
22 September 1906

1907
Carlton (2)
South Melbourne (2)
6.14 (50) d. 6.9 (45)
Melbourne Cricket Ground
45,477
21 September 1907

1908
Carlton (3)
Essendon (3)
5.5 (35) d. 3.8 (26)
Melbourne Cricket Ground
50,261
26 September 1908

1909
South Melbourne
Carlton (2)
4.14 (38) d. 4.12 (36)
Melbourne Cricket Ground
37,759
2 October 1909

1910
Collingwood (3)
Carlton (3)
9.7 (61) d. 6.11 (47)
Melbourne Cricket Ground
42,790
1 October 1910

1911
Essendon (3)
Collingwood (3)
5.11 (41) d. 4.11 (35)
Melbourne Cricket Ground
43,905
23 September 1911

1912
Essendon (4)
South Melbourne (3)
5.17 (47) d. 4.9 (33)
Melbourne Cricket Ground
54,434
28 September 1912

1913
Fitzroy (5)
St Kilda
7.14 (56) d. 5.13 (43)
Melbourne Cricket Ground
59,556
27 September 1913

1914
Carlton (4)
South Melbourne (4)
6.9 (45) d. 4.15 (39)
Melbourne Cricket Ground
30,495
26 September 1914

1915
Carlton (5)
Collingwood (4)
11.12 (78) d. 6.9 (45)
Melbourne Cricket Ground
39,343
18 September 1915

1916
Fitzroy (6)
Carlton (4)
12.13 (85) d. 8.8 (56)
Melbourne Cricket Ground
21,130
2 September 1916

1917
Collingwood (4)
Fitzroy (4)
9.20 (74) d. 5.9 (39)
Melbourne Cricket Ground
25,512
22 September 1917

1918
South Melbourne (2)
Collingwood (5)
9.8 (62) d. 7.15 (57)
Melbourne Cricket Ground
39,262
7 September 1918

1919
Collingwood (5)
Richmond
11.12 (78) d. 7.11 (53)
Melbourne Cricket Ground
45,413
11 October 1919

1920
Richmond
Collingwood (6)
7.10 (52) d. 5.5 (35)
Melbourne Cricket Ground
53,908
2 October 1920

1921
Richmond (2)
Carlton (5)
5.6 (36) d. 4.8 (32)
Melbourne Cricket Ground
43,122
15 October 1921

1922
Fitzroy (7)
Collingwood (7)
11.13 (79) d. 9.14 (68)
Melbourne Cricket Ground
50,054
14 October 1922

1923
Essendon (5)
Fitzroy (5)
8.15 (63) d. 6.10 (46)
Melbourne Cricket Ground
46,566
20 October 1923

1924
Essendon (6)
Richmond (2)
N/A
N/A
N/A
N/A

1925
Geelong
Collingwood (8)
10.19 (79) d. 9.15 (69)
Melbourne Cricket Ground
64,288
10 October 1925

1926
Melbourne (2)
Collingwood (9)
17.17 (119) d. 9.8 (62)
Melbourne Cricket Ground
59,632
9 October 1926

1927
Collingwood (6)
Richmond (3)
2.13 (25) d. 1.7 (13)
Melbourne Cricket Ground
34,551
1 October 1927

1928
Collingwood (7)
Richmond (4)
13.18 (96) d. 9.9 (63)
Melbourne Cricket Ground
50,026
29 September 1928

1929
Collingwood (8)
Richmond (5)
11.13 (79) d. 7.8 (50)
Melbourne Cricket Ground
63,336
28 September 1929

1930
Collingwood (9)
Geelong (2)
14.16 (100) d. 9.16 (70)
Melbourne Cricket Ground
45,022
11 October 1930

1931
Geelong (2)
Richmond (6)
9.14 (68) d. 7.6 (48)
Melbourne Cricket Ground
60,712
10 October 1931

1932
Richmond (3)
Carlton (6)
13.14 (92) d. 12.11 (83)
Melbourne Cricket Ground
69,724
1 October 1932

1933
South Melbourne (3)
Richmond (7)
9.17 (71) d. 4.5 (29)
Melbourne Cricket Ground
75,754
30 September 1933

1934
Richmond (4)
South Melbourne (5)
19.14 (128) d. 12.17 (89)
Melbourne Cricket Ground
65,335
13 October 1934

1935
Collingwood (10)
South Melbourne (6)
11.12 (78) d. 7.16 (58)
Melbourne Cricket Ground
54,154
5 October 1935

1936
Collingwood (11)
South Melbourne (7)
11.23 (89) d. 10.18 (78)
Melbourne Cricket Ground
74,091
3 October 1936

1937
Geelong (3)
Collingwood (10)
18.14 (122) d. 12.18 (90)
Melbourne Cricket Ground
88,540
25 September 1937

1938
Carlton (6)
Collingwood (11)
15.10 (100) d. 13.7 (85)
Melbourne Cricket Ground
96,486
24 September 1938

1939
Melbourne (3)
Collingwood (12)
21.22 (148) d. 14.11 (95)
Melbourne Cricket Ground
78,110
30 September 1939

1940
Melbourne (4)
Richmond (8)
15.17 (107) d. 10.8 (68)
Melbourne Cricket Ground
70,330
28 September 1940

1941
Melbourne (5)
Essendon (4)
19.13 (127) d. 13.20 (98)
Melbourne Cricket Ground
79,687
27 September 1941

1942
Essendon (7)
Richmond (9)
19.18 (132) d. 11.13 (79)
Princes Park
49,000
19 September 1942

1943
Richmond (5)
Essendon (5)
12.14 (86) d. 11.15 (81)
Princes Park
42,100
25 September 1943

1944
Fitzroy (8)
Richmond (10)
9.12 (66) d. 7.9 (51)
Junction Oval
43,000
30 September 1944

1945
Carlton (7)
South Melbourne (8)
15.13 (103) d. 10.15 (75)
Princes Park
62,986
29 September 1945

1946
Essendon (8)
Melbourne
22.18 (150) d. 13.9 (87)
Melbourne Cricket Ground
73,743
5 October 1946

1947
Carlton (8)
Essendon (6)
13.8 (86) d. 11.19 (85)
Melbourne Cricket Ground
85,815
27 September 1947

1948
Melbourne (6)
Essendon (7)
10.9 (69) drew 7.27 (69)
Melbourne Cricket Ground
85,658
2 October 1948

13.11 (89) d. 7.8 (50)
Melbourne Cricket Ground
52,226
9 October 1948

1949
Essendon (9)
Carlton (7)
18.17 (125) d. 6.16 (52)
Melbourne Cricket Ground
90,453
24 September 1949

1950
Essendon (10)
North Melbourne
13.14 (92) d. 7.12 (54)
Melbourne Cricket Ground
87,601
23 September 1950

1951
Geelong (4)
Essendon (8)
11.15 (81) d. 10.10 (70)
Melbourne Cricket Ground
84,109
29 September 1951

1952
Geelong (5)
Collingwood (13)
13.8 (86) d. 5.10 (40)
Melbourne Cricket Ground
81,304
27 September 1952

1953
Collingwood (12)
Geelong (3)
11.11 (77) d. 8.17 (65)
Melbourne Cricket Ground
89,060
26 September 1953

1954
Footscray
Melbourne (2)
15.12 (102) d. 7.9 (51)
Melbourne Cricket Ground
80,897
25 September 1954

1955
Melbourne (7)
Collingwood (14)
8.16 (64) d. 5.6 (36)
Melbourne Cricket Ground
88,053
17 September 1955

1956
Melbourne (8)
Collingwood (15)
17.19 (121) d. 6.12 (48)
Melbourne Cricket Ground
115,803
15 September 1956

1957
Melbourne (9)
Essendon (9)
17.14 (116) d. 7.13 (55)
Melbourne Cricket Ground
100,324
21 September 1957

1958
Collingwood (13)
Melbourne (3)
12.10 (82) d. 9.10 (64)
Melbourne Cricket Ground
97,956
20 September 1958

1959
Melbourne (10)
Essendon (10)
17.13 (115) d. 11.12 (78)
Melbourne Cricket Ground
103,506
26 September 1959

1960
Melbourne (11)
Collingwood (16)
8.14 (62) d. 2.2 (14)
Melbourne Cricket Ground
97,457
24 September 1960

1961
Hawthorn
Footscray
13.16 (94) d. 7.9 (51)
Melbourne Cricket Ground
107,935
23 September 1961

1962
Essendon (11)
Carlton (8)
13.12 (90) d. 8.10 (58)
Melbourne Cricket Ground
98,385
29 September 1962

1963
Geelong (6)
Hawthorn
15.19 (109) d. 8.12 (60)
Melbourne Cricket Ground
101,452
5 October 1963

1964
Melbourne (12)
Collingwood (17)
8.16 (64) d. 8.12 (60)
Melbourne Cricket Ground
102,469
19 September 1964

1965
Essendon (12)
St Kilda (2)
14.21 (105) d. 9.16 (70)
Melbourne Cricket Ground
104,846
25 September 1965

1966
St Kilda
Collingwood (18)
10.14 (74) d. 10.13 (73)
Melbourne Cricket Ground
101,655
24 September 1966

1967
Richmond (6)
Geelong (4)
16.18 (114) d. 15.15 (105)
Melbourne Cricket Ground
109,396
23 September 1967

1968
Carlton (9)
Essendon (11)
7.14 (56) d. 8.5 (53)
Melbourne Cricket Ground
116,828
28 September 1968

1969
Richmond (7)
Carlton (9)
12.13 (85) d. 8.12 (60)
Melbourne Cricket Ground
119,165
27 September 1969

1970
Carlton (10)
Collingwood (19)
17.9 (111) d. 14.17 (101)
Melbourne Cricket Ground
121,696
26 September 1970

1971
Hawthorn (2)
St Kilda (3)
12.10 (82) d. 11.9 (75)
Melbourne Cricket Ground
118,192
25 September 1971

1972
Carlton (11)
Richmond (11)
28.9 (177) d. 22.18 (150)
Melbourne Cricket Ground
112,393
7 October 1972

1973
Richmond (8)
Carlton (10)
16.20 (116) d. 12.14 (86)
Melbourne Cricket Ground
116,956
29 September 1973

1974
Richmond (9)
North Melbourne (2)
18.20 (128) d. 13.9 (87)
Melbourne Cricket Ground
113,839
28 September 1974

1975
North Melbourne
Hawthorn (2)
19.8 (122) d. 9.13 (67)
Melbourne Cricket Ground
110,551
27 September 1975

1976
Hawthorn (3)
North Melbourne (3)
13.22 (100) d. 10.10 (70)
Melbourne Cricket Ground
110,143
25 September 1976

1977
North Melbourne (2)
Collingwood (20)
9.22 (76) drew 10.16 (76)
Melbourne Cricket Ground
108,224
24 September 1977

21.25 (151) d. 19.10 (124)
Melbourne Cricket Ground
98,366
1 October 1977

1978
Hawthorn (4)
North Melbourne (4)
18.13 (121) d. 15.13 (103)
Melbourne Cricket Ground
101,704
30 September 1978

1979
Carlton (12)
Collingwood (21)
11.16 (82) d. 11.11 (77)
Melbourne Cricket Ground
113,545
29 September 1979

1980
Richmond (10)
Collingwood (22)
23.21 (159) d. 9.24 (78)
Melbourne Cricket Ground
113,461
27 September 1980

1981
Carlton (13)
Collingwood (23)
12.20 (92) d. 10.12 (72)
Melbourne Cricket Ground
112,964
26 September 1981

1982
Carlton (14)
Richmond (12)
14.19 (103) d. 12.13 (85)
Melbourne Cricket Ground
107,537
25 September 1982

1983
Hawthorn (5)
Essendon (12)
20.20 (140) d. 8.9 (57)
Melbourne Cricket Ground
110,332
24 September 1983

1984
Essendon (13)
Hawthorn (3)
14.21 (105) d. 12.9 (81)
Melbourne Cricket Ground
92,685
29 September 1984

1985
Essendon (14)
Hawthorn (4)
26.14 (170) d. 14.8 (92)
Melbourne Cricket Ground
100,042
28 September 1985

1986
Hawthorn (6)
Carlton (11)
16.14 (110) d. 9.14 (68)
Melbourne Cricket Ground
101,861
27 September 1986

1987
Carlton (15)
Hawthorn (5)
15.14 (104) d. 9.17 (71)
Melbourne Cricket Ground
92,754
26 September 1987

1988
Hawthorn (7)
Melbourne (4)
22.20 (152) d. 6.20 (56)
Melbourne Cricket Ground
93,754
24 September 1988

1989
Hawthorn (8)
Geelong (5)
21.18 (144) d. 21.12 (138)
Melbourne Cricket Ground
94,796
30 September 1989

Australian Football League name adopted

1990
Collingwood (14)
Essendon (13)
13.11 (89) d. 5.11 (41)
Melbourne Cricket Ground
98,944
6 October 1990

1991
Hawthorn (9)
West Coast
20.19 (139) d. 13.8 (86)
VFL Park
75,230
28 September 1991

1992
West Coast
Geelong (6)
16.17 (113) d. 12.13 (85)
Melbourne Cricket Ground
95,007
26 September 1992

1993
Essendon (15)
Carlton (12)
20.13 (133) d. 13.11 (89)
Melbourne Cricket Ground
96,862
25 September 1993

1994
West Coast (2)
Geelong (7)
20.23 (143) d. 8.15 (63)
Melbourne Cricket Ground
93,860
1 October 1994

1995
Carlton (16)
Geelong (8)
21.15 (141) d. 11.14 (80)
Melbourne Cricket Ground
93,670
30 September 1995

1996
North Melbourne (3)
Sydney (9)
19.17 (131) d. 13.10 (88)
Melbourne Cricket Ground
93,102
28 September 1996

1997
Adelaide
St Kilda (4)
19.11 (125) d. 13.16 (94)
Melbourne Cricket Ground
99,645
27 September 1997

1998
Adelaide (2)
North Melbourne (5)
15.15 (105) d. 8.22 (70)
Melbourne Cricket Ground
94,431
26 September 1998

1999
North Melbourne (4)
Carlton (13)
19.10 (124) d. 12.17 (89)
Melbourne Cricket Ground
94,228
25 September 1999

2000
Essendon (16)
Melbourne (5)
19.21 (135) d. 11.9 (75)
Melbourne Cricket Ground
96,249
2 September 2000

2001
Brisbane Lions
Essendon (14)
15.18 (108) d. 12.10 (82)
Melbourne Cricket Ground
91,482
29 September 2001

2002
Brisbane Lions (2)
Collingwood (24)
10.15 (75) d. 9.12 (66)
Melbourne Cricket Ground
91,817
28 September 2002

2003
Brisbane Lions (3)
Collingwood (25)
20.14 (134) d. 12.12 (84)
Melbourne Cricket Ground
79,451
27 September 2003

2004
Port Adelaide
Brisbane Lions
17.11 (113) d. 10.13 (73)
Melbourne Cricket Ground
77,671
25 September 2004

2005
Sydney (4)
West Coast (2)
8.10 (58) d. 7.12 (54)
Melbourne Cricket Ground
91,828
24 September 2005

2006
West Coast (3)
Sydney (10)
12.13 (85) d. 12.12 (84)
Melbourne Cricket Ground
97,431
30 September 2006

2007
Geelong (7)
Port Adelaide
24.19 (163) d. 6.8 (44)
Melbourne Cricket Ground
97,302
29 September 2007

2008
Hawthorn (10)
Geelong (9)
18.7 (115) d. 11.23 (89)
Melbourne Cricket Ground
100,012
27 September 2008

2009
Geelong (8)
St Kilda (5)
12.8 (80) d. 9.14 (68)
Melbourne Cricket Ground
99,251
26 September 2009

2010
Collingwood (15)
St Kilda (6)
9.14 (68) drew 10.8 (68)
Melbourne Cricket Ground
100,016
25 September 2010

16.12 (108) d. 7.10 (52)
Melbourne Cricket Ground
93,853
2 October 2010

2011
Geelong (9)
Collingwood (26)
18.11 (119) d. 12.9 (81)
Melbourne Cricket Ground
99,537
1 October 2011

2012
Sydney (5)
Hawthorn (6)
14.7 (91) d. 11.15 (81)
Melbourne Cricket Ground
99,683
29 September 2012

2013
Hawthorn (11)
Fremantle
11.11 (77) d. 8.14 (62)
Melbourne Cricket Ground
100,007
28 September 2013

2014
Hawthorn (12)
Sydney (11)
21.11 (137) d. 11.8 (74)
Melbourne Cricket Ground
99,454
27 September 2014

2015
Hawthorn (13)
West Coast (3)
16.11 (107) d. 8.13 (61)
Melbourne Cricket Ground
98,633
3 October 2015

2016
Western Bulldogs (2)
Sydney (12)
13.11 (89) d. 10.7 (67)
Melbourne Cricket Ground
99,981
1 October 2016

2017
Richmond (11)
Adelaide
16.12 (108) d. 8.12 (60)
Melbourne Cricket Ground
100,021
30 September 2017

2018
West Coast (4)
Collingwood (27)
11.13 (79) d. 11.8 (74)
Melbourne Cricket Ground
100,022
29 September 2018

tag: table

text: Minor grade premierships[edit]

text: In addition to the seniors, VFL/AFL clubs have competed in premierships in three minor grades:

text:
VFL/AFL Reserves premierships: 1919–1999
VFL/AFL Under-19s premierships: 1946–1991
VFL/AFL Night premierships: 1956–1971, 1977–2013

tag: ul

text: VFL/AFL Reserves premierships[edit]

text: The reserve grade premiership was held in various formats between 1919 and 1999. It was known as the Victorian Junior Football League from 1919 until 1923, the Seconds from 1924 until 1959, the VFL Reserves from 1960 until 1989, and as the AFL reserves from 1990 until 1999.[7] Until 1991, the competition was run by the VFL/AFL, and from 1992 until 1999 it was administered by the Victorian State Football League.

text:
Season

Premiers

Runners-up

Score [8]

Venue

Attendance

Date

1919
Collingwood (1)
University-A (1)
6.11 (47) d. 4.8 (32)
Melbourne Cricket Ground
45,413 (C-R)
11 October 1919

1920
Collingwood (2)
University (2)
7.14 (56) d. 7.2 (44)
Melbourne Cricket Ground
58,255 (C-R)
25 September 1920

1921
Essendon (1)
Collingwood (1)
10.9 (69) d. 8.13 (61)
Melbourne Cricket Ground
43,122 (C-R)
15 October 1921

1922
Collingwood (3)
Essendon (1)
8.10 (58) d. 1.9 (15)
Melbourne Cricket Ground
50,054 (C-R)
14 October 1922

1923
Geelong (1)
Richmond (1)
9.12 (66) d. 5.10 (40)
Melbourne Cricket Ground
46,566 (C-R)
20 October 1923

1924
Geelong (2)
Essendon (2)
Geelong won on forfeit
Kardinia Park
N/A
N/A

1925
Collingwood (4)
Fitzroy (1)
13.16 (94) d. 11.4 (70)
Melbourne Cricket Ground
64,288 (C-R)
10 October 1925

1926
Carlton (1)
Geelong (1)
14.11 (95) d. 5.13 (43)
Melbourne Cricket Ground
59,632 (C-R)
9 October 1926

1927
Carlton (2)
South Melbourne (1)
12.22 (94) d. 11.9 (75)
Melbourne Cricket Ground
4,210
8 October 1927

1928
Carlton (3)
Geelong (2)
18.18 (126) d. 14.11 (95)
Melbourne Cricket Ground
8,000
27 September 1928

1929
Richmond (1)
Geelong (3)
12.8 (80) d. 7.15 (57)
Melbourne Cricket Ground
6,544
26 September 1929

1930
Geelong (3)
Richmond (2)
14.12 (96) d. 11. (74)
Melbourne Cricket Ground
41,495 (C-R)
4 October 1930

1931
Melbourne (1)
Geelong (4)
8.13 (61) d. 8.5 (53)
Melbourne Cricket Ground
60,712 (C-R)
10 October 1931

1932
Melbourne (2)
Essendon (3)
8.12 (60) d. 4.10 (34)
Melbourne Cricket Ground
69,724 (C-R)
1 October 1932

1933
Melbourne (3)
St Kilda (1)
10.15 (75) d. 10.14 (74)
Melbourne Cricket Ground
9,500
28 September 1933

1934
Melbourne (4)
Geelong (5)
15.18 (108) d. 12.4 (76)
Melbourne Cricket Ground
65,335 (C-R)
13 October 1934

1935
Melbourne (5)
Geelong (6)
12.11 (83) d. 9.6 (60)
Melbourne Cricket Ground
54,154 (C-R)
5 October 1935

1936
Footscray (1)
Melbourne (1)
15.11 (101) d. 6.14 (50)
Melbourne Cricket Ground
74,091 (C-R)
3 October 1936

1937
Geelong (4)
Collingwood (2)
12.12 (84) d. 9.11 (65)
Melbourne Cricket Ground

30 September 1937

1938
Geelong (5)
Footscray (1)
12.19 (91) d. 12.8 (80)
Melbourne Cricket Ground
5,500
29 September 1938

1939
Melbourne (6)
Richmond (2)
22.12 (144) d. 17.13 (115)
Melbourne Cricket Ground
4,100
28 September 1939

1940
Collingwood (5)
Carlton (1)
6.16 (52) d. 3.12 (30)
Melbourne Cricket Ground
70,330 (C-R)
28 September 1940

1941
Essendon (2)
Fitzroy (2)
12.16 (88) d.9.17 (71)
Melbourne Cricket Ground
79,687 (C-R)
27 September 1941

1942
St Kilda (1)
Fitzroy (3)
13.10 (88) d. 7.15 (57)
Punt Road Oval

12 September 1942

1943
St Kilda (2)
Fitzroy (4)
11.14 (80) d. 8.6 (54)
Victoria Park

18 September 1943

1944
Fitzroy (1)
Collingwood (3)
11.12 (78) d. 9.9 (63)
Victoria Park
7,500
23 September 1944

1945
Footscray (2)
Fitzroy (5)
9.16 (70) d. 9.3 (57)
Victoria Park
6,500
22 September 1945

1946
Richmond (2)
Fitzroy (6)
7.15 (57) d. 7.14 (56)
Melbourne Cricket Ground
59,444 (C-R)
28 September 1946

1947
North Melbourne (1)
Richmond (3)
16.13 (109) d. 14.10 (94)
Melbourne Cricket Ground
85,815 (C-R)
27 September 1947

1948
Geelong (6)
Richmond (4)
17.12 (114) d. 12.9 (81)
Melbourne Cricket Ground
86,198 (C-R)
2 October 1948

1949
Melbourne (7)
Essendon (4)
17.10 (112) d. 9.14 (68)
Melbourne Cricket Ground
90,453 (C-R)
24 September 1949

text:
1950 Essendon (3)
1951 Carlton (4)
1952 Essendon (4)
1953 Carlton (5)
1954 Richmond (3)
1955 Richmond (4)
1956 Melbourne (8)
1957 North Melbourne (2)
1958 Hawthorn (1)
1959 Hawthorn (2)

1960 Geelong (7)
1961 St Kilda (3)
1962 Footscray (3)
1963 Geelong (8)
1964 Geelong (9)
1965 Collingwood (6)
1966 Richmond (5)
1967 North Melbourne (3)
1968 Essendon (5)
1969 Melbourne (9)

1970 Melbourne (10)
1971 Richmond (6)
1972 Hawthorn (3)
1973 Richmond (7)
1974 Fitzroy (2)
1975 Geelong (10)
1976 Collingwood (7)
1977 Richmond (8)
1978 North Melbourne (4)
1979 North Melbourne (5)

1980 Geelong (11)
1981 Geelong (12)
1982 Geelong (13)
1983 Essendon (6)
1984 Melbourne (11)
1985 Hawthorn (4)
1986 Carlton (6)
1987 Carlton (7)
1988 Footscray (4)
1989 Fitzroy (3)

1990 Carlton (8)
1991 Brisbane Bears (1)
1992 Essendon (7)[9]
1993 Melbourne (12)[10]
1994 Footscray (5)[11]
1995 North Melbourne (6)[12]
1996 North Melbourne (7)[13]
1997 Richmond (9)[14]
1998 Western Bulldogs (6)[15]
1999 Essendon (8)[16]
Source where unlisted[17]

text: VFL/AFL Under-19s premierships[edit]

text: The VFL/AFL's Under-19s competition was held between 1946 and 1991. It was known as the VFL Thirds until 1959, and as the Under-19s thereafter.[7]

text:
Season

Premiers

Runners-up

Score [18]

Venue

Attendance

Date

1946
North Melbourne (1)
Carlton (1)
11.9 (75) d. 5.12 (42)

21 September 1946

1947
Melbourne (1)
North Melbourne (1)
12.13 (85) d. 11.7 (73)

6 September 1947

1948
Carlton (1)
Essendon (1)
6.10 (46) d. 5.6 (36)

1949
Carlton (2)
Geelong (1)
9.8 (62) d. 7.9 (51)

text:
1950 Essendon (1)
1951 Carlton (3)
1952 Essendon (2)
1953 Melbourne (2)
1954 Footscray (1)
1955 Fitzroy (1)
1956 South Melbourne (1)
1957 St Kilda (1)
1958 Richmond (1)
1959 Essendon (3)

1960 Collingwood (1)
1961 Essendon (4)
1962 Geelong (1)
1963 Carlton (4)
1964 Melbourne (3)
1965 Collingwood (2)
1966 Essendon (5)
1967 Richmond (2)
1968 Richmond (3)
1969 Richmond (4)

1970 Richmond (5)
1971 Melbourne (4)
1972 Hawthorn (1)
1973 Richmond (6)
1974 Collingwood (3)
1975 Richmond (7)
1976 North Melbourne (2)
1977 Richmond (8)
1978 Carlton (5)
1979 Carlton (6)

1980 Richmond (9)
1981 Melbourne (5)
1982 Fitzroy (2)
1983 Melbourne (6)
1984 North Melbourne (3)
1985 Richmond (10)
1986 Collingwood (4)
1987 North Melbourne (4)
1988 North Melbourne (5)
1989 Richmond (11)

1990 North Melbourne (6)
1991 North Melbourne (7)
Source[17]

text: VFL/AFL Night premierships[edit]

text: The pre-season and night premiership covers three competitions which are considered historically equivalent in status:

text:
VFL Night Series, a consolation competition played amongst non-finalists between 1956 and 1971.
Australian Football Championships Night Series, a mid-season knock-out competition played concurrently with the premiership and involving teams from interstate, played between 1977 and 1987.
Australian Football League pre-season competition, played before each season from 1988 until 2013.

text: For a list of premiers in these competitions, see list of Australian Football League pre-season and night series premiers.

text: Premierships by team[edit]

text:
Club

Years in competition

Premierships

Runners-up

Premiership years

Runner-up years

Essendon
1897–present
16
14
1897, 1901, 1911, 1912, 1923, 1924, 1942, 1946, 1949, 1950, 1962, 1965, 1984, 1985, 1993, 2000
1898, 1902, 1908, 1941, 1943, 1947, 1948, 1951, 1957, 1959, 1968, 1983, 1990, 2001

Carlton
1897–present
16
13
1906, 1907, 1908, 1914, 1915, 1938, 1945, 1947, 1968, 1970, 1972, 1979, 1981, 1982, 1987, 1995
1904, 1909, 1910, 1916, 1921, 1932, 1949, 1962, 1969, 1973, 1986, 1993, 1999

Collingwood
1897–present
15
27
1902, 1903, 1910, 1917, 1919, 1927, 1928, 1929, 1930, 1935, 1936, 1953, 1958, 1990, 2010
1901, 1905, 1911, 1915, 1918, 1920, 1922, 1925, 1926, 1937, 1938, 1939, 1952, 1955, 1956, 1960, 1964, 1966, 1970, 1977, 1979, 1980, 1981, 2002, 2003, 2011, 2018

Hawthorn
1925–present
13
6
1961, 1971, 1976, 1978, 1983, 1986, 1988, 1989, 1991, 2008, 2013, 2014, 2015
1963, 1975, 1984, 1985, 1987, 2012

Melbourne
1897–present
12
5
1900, 1926, 1939, 1940, 1941, 1948, 1955, 1956, 1957, 1959, 1960, 1964
1946, 1954, 1958, 1988, 2000

Richmond
1908–present
11
12
1920, 1921, 1932, 1934, 1943, 1967, 1969, 1973, 1974, 1980, 2017
1919, 1924, 1927, 1928, 1929, 1931, 1933, 1940, 1942, 1944, 1972, 1982

Geelong
1897–present
9
9
1925, 1931, 1937, 1951, 1952, 1963, 2007, 2009, 2011
1897, 1930, 1953, 1967, 1989, 1992, 1994, 1995, 2008

Fitzroy
1897–1996
8
5
1898, 1899, 1904, 1905, 1913, 1916, 1922, 1944
1900, 1903, 1906, 1917, 1923

South Melbourne / Sydney
1897–present
5
12
1909, 1918, 1933, 2005, 2012
1899, 1907, 1912, 1914, 1934, 1935, 1936, 1945, 1996, 2006, 2014, 2016

North Melbourne
1925–present
4
5
1975, 1977, 1996, 1999
1950, 1974, 1976, 1978, 1998

West Coast
1987–present
4
3
1992, 1994, 2006, 2018
1991, 2005, 2015

Brisbane Lions
1997–present
3
1
2001, 2002, 2003
2004

Adelaide
1991–present
2
1
1997, 1998
2017

Footscray / Western Bulldogs
1925–present
2
1
1954, 2016
1961

St Kilda
1897–present
1
6
1966
1913, 1965, 1971, 1997, 2009, 2010

Port Adelaide
1997–present
1
1
2004
2007

Fremantle
1995–present
0
1

2013

University
1908–1914
0
0

Brisbane Bears
1987–1996
0
0

Gold Coast
2011–present
0
0

Greater Western Sydney
2012–present
0
0


document_title: Romeo + Juliet

question_text: where was baz luhrmann's romeo and juliet filmed

question_tokens: where was baz luhrmann 's romeo and juliet filmed

text: Romeo + Juliet

text: Plot[edit]

text: In Verona Beach, the Capulets and the Montagues are arch-rivals.[5] The animosity of the older generation—Fulgencio and Gloria Capulet and Ted and Caroline Montague—is felt by their younger relatives. A gunfight between the Montague boys led by Benvolio, Romeo's cousin, and the Capulet boys led by Tybalt, Juliet's cousin, creates chaos in the city. The Chief of Police, Captain Prince, reprimands the families, warning them that if such behavior continues, their lives "shall pay the forfeit of the peace".

text: Benvolio meets Romeo on a beach. While playing a game of pool they learn of a party being held by the Capulets that evening which they decide to gate-crash. Romeo agrees to come after discovering that Rosaline, with whom he is in love, is attending.

text: The Montague boys meet their friend, Mercutio, who has tickets to the Capulet party. Romeo takes the ecstasy Mercutio gave him and they proceed to the Capulet mansion. The effects of the drug and the party overwhelm Romeo, who goes to the restroom. While admiring an aquarium, he and Juliet see each other and fall instantly in love. Tybalt spots Romeo and vows to kill him for invading his family's home, but Fulgencio stops him.

text: Romeo and Juliet sneak into an elevator and kiss. The nurse spots them when the doors open and drags Juliet away, while revealing to her that Romeo is a Montague. At the same time, Romeo realizes that Juliet is a Capulet. Mercutio takes Romeo from the party, but he sneaks back to the mansion, hiding under Juliet’s balcony. Juliet emerges into the yard and proclaims her love for him before Romeo sneaks up behind her. Juliet warns him that he is risking his life, but Romeo tells her he does not care whether he is caught. Knowing her nurse is looking for her, Juliet tells him that, if he sends word by the following day, they will be betrothed. Romeo visits Father Lawrence, telling him he wants to marry Juliet. He agrees to marry the pair in hopes that their marriage will help ease the tensions between the families. Romeo passes the word on to Juliet’s nurse and the lovers are married.

text: Tybalt encounters Mercutio just as Romeo arrives. Romeo attempts to make peace, but Tybalt assaults him. Mercutio intervenes and batters Tybalt, and is about to finish him off by hitting him with a heavy stick when Romeo stops him. Tybalt then wounds Mercutio with a shard of glass, which Mercutio claims is merely "a scratch". But as he realizes the cut is much worse than he thought, Mercutio curses both the Montagues and the Capulets before dying in Romeo's arms. Enraged, Romeo chases after a fleeing Tybalt and guns him down.

text: Captain Prince banishes Romeo from the city. Romeo goes into hiding with Father Lawrence, who treats Romeo's injuries and says that, after some time passes, he will help Romeo and Juliet return to the city and reconcile with their family and friends. The nurse tells Romeo that Juliet is waiting for him. When Romeo climbs over Juliet's balcony, she kisses him and they consummate their marriage. Fulgencio decides Juliet will marry Dave Paris, the governor's son.

text: The next morning, Romeo narrowly escapes as Juliet's mother tells her that the family has promised she will marry Paris. She refuses to marry, so her father threatens to disown her. Her mother and nurse insist it would be in her best interest to marry Paris. To get out of this, Juliet runs away from home and sees Father Lawrence, very angrily imploring him to help her and threatening to commit suicide. Father Lawrence proposes she fake her own death and be put in the Capulet vault to awaken 24 hours later. Romeo will be told of the plot, sneak into the vault, and once reunited the two can travel to Mantua. He gives her the potion which mimics death. After saying goodnight to her mother, Juliet drinks the potion and falls into a coma. She is found in the morning, declared dead, and placed in the vault. Balthasar, one of Romeo's cousins, learns that Juliet is dead and tells Romeo, who is not home when the messenger arrives with a letter from Friar Lawrence.

text: Romeo returns to Verona, where he buys poison. As he goes to the church, Captain Prince finds out he is back, and tries to capture him, without success. Father Lawrence learns that Romeo never got his letter and has no idea Juliet is alive. Romeo enters the church where Juliet lies and bids her goodbye. She awakens just as Romeo takes the poison; the two thus see each other before he dies. After he dies, Juliet picks up Romeo's gun and shoots herself in the head, dying instantly. The two lovers are discovered in each other's arms. Prince condemns both families, whose feuding led to such tragedy, while coroners quickly transport the two bodies to the hospital.

text: Cast[edit]

text:
The House of Montague

Brian Dennehy as Ted Montague, Romeo's father[6]
Christina Pickles as Caroline Montague, Romeo's mother
Leonardo DiCaprio as Romeo Montague
Dash Mihok as Benvolio Montague, Romeo's cousin
Jesse Bradford as Balthasar Montague, Romeo's cousin
Zak Orth as Gregory Montague, Romeo's cousin
Jamie Kennedy as Sampson Montague, Romeo's cousin

The House of Capulet

Paul Sorvino as Fulgencio Capulet, Juliet's father
Diane Venora as Gloria Capulet, Juliet's mother
Claire Danes as Juliet Capulet/Juliet Capulet-Montague
John Leguizamo as Tybalt Capulet, Juliet's cousin
Vincent Laresca as Abra Capulet, Juliet's cousin
Carlos Martín Manzo Otálora as Petruchio Capulet, Juliet's cousin
Miriam Margolyes as Nurse, Juliet's nanny

Others

Harold Perrineau as Mercutio, Romeo's best friend
Pete Postlethwaite as Father Lawrence, the priest who marries Romeo and Juliet
Paul Rudd as Dave Paris, the governor's son and Juliet's fiance
Vondie Curtis-Hall as Captain Prince, the chief of police
M. Emmet Walsh as Apothecary
Quindon Tarver as Choir Boy, the singer at Romeo and Juliet's wedding
Edwina Moore as the Anchorwoman, who assumes the role of the Chorus

text: Natalie Portman had been cast as Juliet but, during rehearsals, it was felt that the footage looked as though DiCaprio was "molesting" her.[7] Baz Luhrmann has also stated that Portman was too young at the time, and made DiCaprio look older than intended. He was 21 at the time of filming and Portman was only 14. Rudd, who played Count Paris, Juliet's would-be fiancé, was 26 at the time of filming.[citation needed]

text: DiCaprio proclaimed that Danes should be cast, as he felt she was genuine in her line delivery and did not try to impress him by acting flirtatious.[8]

text: Production[edit]

text: After the success of Strictly Ballroom, Luhrmann took some time over deciding what his next project would be:

text: Our philosophy has always been that we think up what we need in our life, choose something creative that will make that life fulfilling, and then follow that road. With Romeo and Juliet what I wanted to do was to look at the way in which Shakespeare might make a movie of one of his plays if he was a director. How would he make it? We don't know a lot about Shakespeare, but we do know he would make a 'movie' movie. He was a player. We know about the Elizabethan stage and that he was playing for 3000 drunken punters, from the street sweeper to the Queen of England - and his competition was bear-baiting and prostitution. So he was a relentless entertainer and a user of incredible devices and theatrical tricks to ultimately create something of meaning and convey a story. That was what we wanted to do.[9]

text: Luhrmann obtained some funds from Fox to do a workshop and shoot some teaser footage in Sydney. Leonardo DiCaprio agreed to pay his own expenses to fly to Sydney and be part of it. Once Fox saw footage of the fight scene, they agreed to support it.[9]

text: All of the development was done in Australia, with pre-production in Australia and Canada and post-production in Australia. While some parts of the film were shot in Miami, most of the film was shot in Mexico City and Boca del Rio, Veracruz. For instance, the Capulet mansion was set at Chapultepec Castle while the ballroom was built on Stage One of Churubusco Studios; and the church is Immaculate Heart of Mary in the Del Valle neighborhood.[10]

text: Reception[edit]

text: The film premiered on November 1, 1996 in the United States and Canada, in 1,276 theaters, and grossed $11.1 million its opening weekend, ranking #1 at the box office. It went on to gross $46.3 million in the United States and Canada,[11] with a worldwide total of USD$147,554,998.[2]

text: Review aggregator Rotten Tomatoes rated the film "Fresh", with 72% of 53 critics giving positive reviews with an average rating of 6.5/10 with the consensus that says, "Baz Luhrmann's visual aesthetic is as divisive as it is fresh and inventive".[12] James Berardinelli gave the film 3 out of 4 stars and wrote, "Ultimately, no matter how many innovative and unconventional flourishes it applies, the success of any adaptation of a Shakespeare play is determined by two factors: the competence of the director and the ability of the main cast members. Luhrmann, Danes, and DiCaprio place this Romeo and Juliet in capable hands."[13]

text: Leonardo DiCaprio won Favorite Actor and Claire Danes won Favorite Actress in a Romance at the 1997 Blockbuster Entertainment Awards.[4] At the 1997 MTV Movie Awards, Danes won Best Female Performance. DiCaprio was nominated for Best Male Performance, and DiCaprio and Danes were both nominated for Best Kiss and Best On-Screen Duo.[4] At the 51st BAFTA Film Awards, director Baz Luhrmann won Best Direction, Luhrmann and Mary Haile won the Best Adapted Screenplay, Nellee Hooper won the Best Film Music, and Catherine Martin won the Best Production Design. The film was also nominated for Best Cinematography, Best Editing, and Best Sound.[4]

text: The film won several awards.[4] At the 47th Berlin International Film Festival in 1997, DiCaprio won the Silver Bear for Best Actor and Luhrmann won the Alfred Bauer Prize.[3] Luhrmann was also nominated for the Golden Bear Award for Best Picture.[4] At the 69th Academy Awards, Catherine Martin and Brigitte Broch were nominated for Best Art Direction/Set Decoration.[4]

text: Conversely, Roger Ebert gave the film a mixed review of only 2 stars out of 4, saying, "I've seen “King Lear” as a samurai drama and “Macbeth” as a Mafia story, and two different “Romeo and Juliets” about ethnic difficulties in Manhattan (“West Side Story” and “China Girl”), but I have never seen anything remotely approaching the mess that the new punk version of “Romeo & Juliet” makes of Shakespeare's tragedy."[14]

text: The film was nominated to appear on the American Film Institute's 100 Years...100 Passions list in 2002.[15]

text: Soundtrack[edit]

text:
"#1 Crush" – Garbage
"Local God" – Everclear
"Angel" – Gavin Friday
"Pretty Piece of Flesh" – One Inch Punch
"Kissing You (Love Theme from Romeo & Juliet)" – Des'ree
"Whatever (I Had a Dream)" – Butthole Surfers
"Lovefool" – The Cardigans
"Young Hearts Run Free" – Kym Mazelle
"Everybody's Free (To Feel Good)" – Quindon Tarver
"To You I Bestow" – Mundy
"Talk Show Host" – Radiohead
"Little Star" – Stina Nordenstam
"You and Me Song" – The Wannadies
"Layers of Darkness" - Marching Show Concept's Recording
"Exit Music (For a Film)"- Radiohead


document_title: Honda Civic Hybrid

question_text: how many spark plugs in a honda civic hybrid

text: Honda Civic Hybrid

text: First generation (2001–2005)[edit]

text:
First generation

Overview

Production
2001–2005

Model years
2003–2005 (U.S.)

Body and chassis

Related
Honda Civic

Powertrain

Engine
1.3 L LDA series I4 SOHC

Transmission
5-speed manual
CVT automatic

Dimensions

Wheelbase
103.1 in (2,619 mm)

Length
2003: 174.6 in (4,435 mm)
2004–05: 175.4 in (4,455 mm)

Width
67.5 in (1,714 mm)

Height
2003: 56.7 in (1,440 mm)
2004–05: 56.3 in (1,430 mm)

text: The Civic hybrid, based on the seventh generation Civic, was first introduced to the Japanese market in December 2001. Honda claimed it was the most fuel efficient 5-passenger gasoline-powered production vehicle in the world at the time.[1] It was introduced to the U.S. in spring 2002 as a 2003 model. It is the first hybrid vehicle to be certified as an Advanced Technology Partial Zero- Emissions Vehicle (AT-PZEV) from CARB.[2]

text: Design[edit]

text: The first generation of the Honda Civic Hybrid was based on the seventh generation Honda Civic. It was the first mainstream vehicle from Honda equipped with a gasoline-electric hybrid system and became the second hybrid model of the company after Insight. Model with manual transmission was rated city 46 mpg‑US (5.1 L/100 km; 55 mpg‑imp) / highway 51 mpg‑US (4.6 L/100 km; 61 mpg‑imp) according to United States Environmental Protection Agency (EPA) fuel mileage estimates,[3] about the same combined mileage as for the Toyota Prius, and became the most fuel-efficient five-passenger sedan ever sold in North America at the time.[4]

text: The following is a list of its technical features:[5][6][7]

text:
Twin spark plugs light the lean fuel-air mixtures sent to the two-valve combustion chambers.
1.3-litre single overhead cam i-DSI lean-burn internal-combustion engine with VTEC Cylinder Cut-off System, which allows three cylinders to deactivate during deceleration. The engine generates 85 hp (63 kW) at 5,700 rpm and 87 lb⋅ft (118 N⋅m) of torque at 3300 rpm.
Idle stop - when stopped at traffic light, the engine shuts off automatically, then restarts immediately when the driver takes their foot off the brake, contributing to both greater fuel efficiency and lower emissions.
10 kW (13 hp) brushless, permanent magnet assist motor, which functions as a generator during deceleration recharging the battery (regenerative braking).
Combined output of both engine and electric motor is 93 hp (69 kW) at 5,700 rpm. Maximum torque is rated 116 lb⋅ft (157 N⋅m) at 1,500 rpm for manual transmission models and 105 lb⋅ft (142 N⋅m) at 3,000 rpm for CVT models.
144 V Nickel-metal hydride batteries with 6.0 A·h capacity.
Honda Multimatic S continuously variable transmission or 5-speed manual transmission.
ULEV or AT-PZEV certification by the California Air Resources Board (CARB).
Low rolling resistance tires (P185/70R14) on aluminum wheels and regenerative braking.
Electric power-steering.

text: An electric motor is sandwiched between the gasoline engine and the transmission, providing up to 13 horsepower. The motor also acts as a generator, to recharge the car's nickel-metal hydride battery located between the rear seat and the trunk, and as a starter motor.

text: The motor in Civic hybrid is about a quarter-inch (6.4 mm) thicker than that of the Insight. Through improvements to the magnetic coils of the DC brushless motor, it achieves 30 percent greater assisting and regenerative torque than the previous model without increasing the size.

text: It generates more torque (46 versus 36 pound-feet) than the motor in Insight. The electricity is stored in a battery consisting of 120 1.2-volt Ni-MH D-cells wired in series. The battery can charge and discharge more rapidly and efficiently though the total capacity is reduced from the Insight's (6.0 versus 6.5 AH). Efficiency of the battery modules is increased, through a reduction in energy losses. The battery is housed with the electrical controller in a package called the Intelligent Power Unit (IPU). The new packaging reduces the size of the system by 50 percent and allows the IMA equipment be placed behind the rear seat in the trunk. The unit weighs only 63 lb (29 kg) and is one-third smaller than that of the Insight.

text: The two spark plugs in each cylinder can fire either sequentially or simultaneously, enabling more efficient burning during lean-burn mode and more often lean-burn operation. The engine can operate at a lean 22:1 air-to-fuel ratio more than 60 percent of the time on a flat road. The VTEC cylinder idling system of the engine closes the valves in three of the four cylinders when the car is decelerating, reduces the power lost to the engine by 50 percent, and allows the IMA to extract more electrical energy during braking. The rocker arms operating the intake and exhaust valves have two modes: valve-lift mode or idle mode. They are engaged via a synchronizing piston. During deceleration, the synchro piston disengages the lift-mode rocker arm so that the valves remain at rest, effectively sealing off the cylinder.

text: An idle stop feature shuts off the engine automatically when stopped, then restarts immediately when the driver removes their foot from the brake. This auto idle stop system contributes to both greater fuel efficiency and lower emissions. During stop and go driving, the engine will turn off when the car comes to a stop for the first time, however, if the car does not go above 10 mph (16 km/h) and stops again, the engine will not turn off unless the car is stopped for more than 15 seconds.[8]

text: With assistance from the electric motor, the combined torque at below 3,700 rpm is greater than that available from the non-hybrid Civic's 1.7-liter engine.

text: Fuel efficiency is further improved by six percent by utilizing: a new front air dam and rear spoiler, along with revised underbody panels, reducing the drag coefficient from 0.30 to 0.28; replacing traditional power steering with electrical power result as reduction in parasitic losses and special lower rolling resistance tires. The Dunlop tires improve ride quality and reduce road noise compared with other hybrids like Insight and Prius. When compared with Insight, a wider tire improves stability at highway speed. Car and Driver reported that the car can accelerate 0–60 mph (0–97 km/h) in 10.9 seconds.

text: Fuel economy[edit]

text: The Civic hybrid is estimated to be 40 percent more fuel efficient than its non-hybrid counterpart.[9]

text: Award and recognition[edit]

text:
The Civic Hybrid's engine won the International Engine of the Year "1 litre to 1.4 litre" size category award for three years straight from 2002 through 2004 as well as the "Best Fuel Economy" category for 2003 and 2004.[citation needed]
2003 recognized by the American Council for an Energy Efficient Economy amongst the top ten Greenest Vehicles: tied for the third best score with Toyota Prius[10]

text: Minor Design Changes[edit]

text: There was a minor refresh of the design between the 2003 and 2004 model years which affected the front and rear bumper covers, hood and head lights. On the interior, a small center console replaced the driver's arm rest and the rear seats got adjustable head rests. [11]

text: Second generation (2006–2011)[edit]

text:
Second generation

Overview

Production
2005–2011

Model years
2006–2011

Body and chassis

Related
Honda Civic

Powertrain

Engine
Gasoline: 1.3 L LDA series I4 SOHC
Electric: 158 volt 15 kW

Transmission
CVT automatic

Dimensions

Wheelbase
106.3 in (2,700 mm)

Length

2006–08: 176.7 in (4,488 mm)(USDM)
2006–08: 4,540 mm (178.7 in)(JDM)
2009: 177.3 in (4,503 mm)

Width
69.0 in (1,753 mm)

Height
56.3 in (1,430 mm)

Curb weight
1,305 kg (2,877 lb)(USDM)
1,260 kg (2,778 lb)(JDM)

text: The second generation Civic Hybrid is based on the eighth generation Civic. As with other Civics, there are some styling differences to the exterior between the North American and the Japanese market models.

text: Design[edit]

text: The powertrain of the second generation Civic hybrid is similar to that of the first generation.

text: The following is a list of major changes:

text:
Updated to fourth generation Integrated Motor Assist (IMA)
More powerful electric motor of 20 hp (15 kW)
158.4 V (132 x 1.2 V) Nickel-metal hydride batteries with 5.5 A·h capacity that is 12% smaller.
Updated to three stage i-VTEC and VCM (Variable Cylinder Management), which permits deactivation of all four cylinders when cruising at moderate speed to run on electric power only. Engine output is increased to 93 hp (69 kW) at 6,000 rpm and maximum torque to 89 lb⋅ft (121 N⋅m) at 4,500 rpm.
Combined output of both engine and motor is 110 hp (82 kW) at 6,000 rpm. Maximum torque is rated 123 lb⋅ft (167 N⋅m) at 2,500 rpm.
A new hybrid compressor for the air-conditioner.
The continuously variable transmission provides a 9% wider range between the maximum and minimum gear ratios for better acceleration and reduced engine rpm at high speeds.
Discontinued manual transmission option.
The U.S. EPA fuel economy estimate is increased to city 49 mpg‑US (4.8 L/100 km), highway 51 mpg‑US (4.6 L/100 km).[12] (In 2008: EPA revised the way it estimates fuel mileage,[13] as a result, the EPA rating for the 2008 model is: city 40 mpg‑US (5.9 L/100 km), highway 45 mpg‑US (5.2 L/100 km)).
Updated to 15-inch lightweight aerodynamic alloy wheels (later featured on the Civic DX-G in Canada as well).
Certified as AT-PZEV throughout 50 states.

text: By using high-performance magnets and high-density windings, Honda is able to increase the power output of the electric motor by 50% to 20 hp (15 kW) at 2,000 rpm when compared with the first generation. The inverter that controls motor speed is integrated with the motor's ECU for more precise control, resulting in greater efficiency and fuel economy. The output of battery is increased by around 30 percent to 158.4 V. The battery storage box is designed for better cooling performance and vibration resistance to enhance long-term reliability. The higher output of electric motor enables the car to run on electricity only, at a steady 15 to 20 mph (24–32 km/h) when cruising on a flat surface.

text: An internal electric motor is added to the air-conditioner, so it can be powered by either the engine, an electric motor, or both. At a stop, the compressor powered by the battery keeps the cabin cool. An additional compressor that is powered by the petrol engine also engages if rapid cooling is required. When the interior temperature is stable, air conditioning is provided by the battery solely. As soon as the brake pedal is lifted, the petrol engine comes back to life again.

text: The new three stage i-VTEC valvetrain has low-rpm, high-rpm and cylinder idle mode. High output valve timing helps the engine to increase its output by 9 percent. During deceleration, the engine is kept idle. There is no combustion in all four cylinders and the cylinders are sealed shut, reducing pumping losses by engine. As a result, recovery of energy wasted during braking is improved by 10 percent.

text: A digital display is incorporated in the instrument dash showing how much electricity is sent to the battery or how much is used. When the car is braked moderately, maximum number of green LEDs light up showing energy recaptured. When the car is braked harder, the conventional brakes are activated.

text: Car and Driver found the car, when compared with previous generation, faster, offered greater refinement, quieter at highway speed, has a stiffer body and a revised suspension that handles bumps better and quietly.[14]

text: Fuel economy[edit]

text: It is estimated that, when compared to a gasoline engine only Civic sedan of 2006 with an automatic transmission, the Civic hybrid provides an increase of fuel economy in city driving of about 63 percent and an increase of fuel economy in highway driving of about 27 percent. The CVT transmission is designed to achieve the highest efficiency for a given RPM.[15]

text: A class-action lawsuit filed in 2012 alleged that Honda falsely advertised the fuel economy of the Civic Hybrid and that owners were getting significantly lower mileage.[16] The Los Angeles Times reported in May 2012 that at least 36 small-claims lawsuits had also been filed against Honda over alleged false advertisement of gas mileage.[17]

text: Some users reported that the fuel economy of the Civic Hybrid was reduced after Honda installed a software update to prolong the life of the hybrid battery by reducing the electric motor's output and putting more reliance on the gasoline engine.[18]

text: Battery life[edit]

text: A Consumer Reports survey found a very high rate of battery failure in Civic Hybrids 2nd-generation Civic Hybrids, describing the failure rate for 2009-2010 models as "shocking", with over 30% of responders reporting they had needed a battery replacement within the last 12 months.[19] Honda acknowledged problems with the 2006-2008 models which could cause the batteries to "deteriorate and eventually fail";[17] software updates were issued to prolong the life of the battery, but some owners reported these updates led to reduced fuel economy and power.[18] The 132 NiMH cell pack suffers from imbalance as individual cells can't be monitored or charged. Monitoring is available at a 12 cell sub-pack level, but charging isn't. After years/miles of use, the cells become imbalanced as the cells charge/discharge at slightly different rates from one another. Eventually, strong cells are limiting the upper capacity of the pack and weak cells are limiting the lower capacity of the pack thereby reducing the usable capacity of the pack. There are higher capacity non-OEM packs available for less than the OEM price, and many owners have achieved years-long extensions of usable battery life by utilizing a grid charger. A grid charger is a home-made or purchased charger that connects your car to the power-grid. These devices impart a long, slow "balancing" charge where all cells are gently charged to their maximum capacity. This can temporarily restore balance and dramatically improve usable capacity for months at a time.

text: In March 2015, Honda sent 2009-2011 owners a letter indicating that all versions, not just the PHEV states, would get the 10 year/150,000 mi warranty on the IMA battery. Reference Service Bulletin #15-006.[20]

text: Market reception[edit]

text: The Civic hybrid ranks as the second best selling electric hybrid car in the U.S.[21]

text: Cost of ownership[edit]

text: Consumer Reports ran an article in April 2006 stating that hybrid vehicles would not pay for themselves over 5 years of ownership. However, there was an error in the calculation of depreciation for the hybrid vehicles. It resulted in overstating how much extra money the hybrids would cost their owners during the first five years of ownership.[22] When corrected, the Honda Civic Hybrid did have a payback period of slightly less than 5 years.[23] In October 2010 Vincentric performed a hybrid cost of ownership analysis for the USA market. In this analysis it compared hybrids' 5-year cost of ownership to their all-gas counterparts. The analysis showed that the 2010 Honda Civic Hybrid cost an additional $1830 over a 2010 Honda Civic EX 2D Coupe with an Automatic Transmission (the report assume 15,000 miles are driven annually and fuel prices are based on a weighted average over the five months prior to October 2010).[24]

text: In August 2010, Autoblog reported that a replacement battery for the Civic Hybrid retailed at $2,100.[25]

text: Other markets[edit]

text: The Civic hybrid was introduced to Malaysia in August 2007.[26] It was launched in China in November 2007 and in India in June 2008.[27]

text: Motorsport[edit]

text: The Honda Civic Hybrid competed in 24 Hours Nürburgring in 2007, finishing 108th out of 220 teams starting. The twenty-four hour race is held around the Nürburgring, one of the world's most grueling courses.[28] A Group N spec Honda Civic hybrid raced in the Jim Clark rally and took second in class.[29]

text: Awards and recognition[edit]

text:
2006 North American Car of the Year, along with the rest of the Civic range[30]
2006 Motor Trend Car of the Year award, along with the rest of the Civic range.[31]
2006 Automotive Journalists Association of Canada (AJAC) Award for Alternative Power Vehicle.[32]
2006 Winner of the World Green Car[33]

text: Third generation (2011–2015)[edit]

text:
Third generation

Overview

Production
2011–2015

Model years
2012–2015

Body and chassis

Related
Honda Civic

Powertrain

Engine
1.5 L water-cooled 4-stroke SOHC i-VTEC+IMA

Transmission
CVT automatic

Hybrid drivetrain
Honda (Integrated Motor Assist) with Eco Assist

Dimensions

Wheelbase
2,670 mm (105 in)

Length
4,525 mm (178 in)

Width
1,755 mm (69 in)

Height
1,430 mm (56 in)

Curb weight
1,280 kg (2,822 lb)

text: The last Civic Hybrid was launched during 2011 in the U.S. and Canada as a 2012 model. It has a larger 1.5-liter i-VTEC engine that produces 90 horsepower and 97 pound-feet of torque[34] and a lithium-ion battery pack instead of nickel-metal hydride. The larger engine replaces the 1.3-L engine for better mid-range torque.[35] The DC brushless permanent magnet motor, which is placed between the engine and continuously variable transmission, provides 17 kW (23 hp) and 78 pound-feet of torque and weighs 0.7 kg (1.5 lb) less.[35] The 2012 Civic Hybrid has an EPA rating of 44 mpg‑US (5.3 L/100 km; 53 mpg‑imp) for the city and highway driving cycles, an improvement from 40 mpg‑US (5.9 L/100 km; 48 mpg‑imp) city and 43 mpg‑US (5.5 L/100 km; 52 mpg‑imp) highway for the previous generation.[36]

text: The Civic Hybrid has the latest Integrated Motor Assist (IMA) parallel hybrid system, with a new 20 kW lithium-ion battery — a first for a Honda hybrid vehicle.[35] The new battery is 5 kW more powerful, 9 kg (20 lb) lighter and takes up 36% less space.[35] Battery capacity is increased from 35 kAh to 100 kAh (4.5 Ah).[35]

text: It comes with improved aerodynamics and Honda ECO Assist technology.[37] The ECO Assist technology is an information system to help the driver adopt a more fuel-efficient driving style,[38] and is proven to improve fuel economy by about 10% for Honda's hybrid vehicles in Japan.[39]

text: Production[edit]

text: Production of the Civic hybrid sedan was moved from Suzuka, Japan to Indiana, United States in early 2013, following the production of the Acura ILX hybrid commenced at Indiana plant in April 2012, after production capacity was expanded to 250,000.[40]

text:
Honda Civic Hybrid sedan (Australia)

Rear view of 2012 Civic Hybrid (US)

Front view of 2013 Civic Hybrid (Thailand)

text: Sales[edit]

text: In February 2009, Honda reported that since 2001 they had sold more than 255,000 Civic Hybrids, including more than 190,000 units sold in North America.[41] For a time, the Civic Hybrid was the second-best-selling hybrid electric car in the U.S.[21]

text:
Cumulative sales by region (as of end January 2009)[41]

Region
Start of sales
Cumulative sales

Japan
Dec 2001
22,899

North America
Mar 2002
191,493

Europe
May 2003
34,757

Asia/Oceania
Feb 2004
5,514

China
Nov 2007
280

Others
May 2006
306

Total (units):
255,249

text: It is reported that over 50,000 Civic Hybrids were sold during 2007 worldwide.[42]

text: Legal actions over mileage claims[edit]

text: In January 2012, Heather Peters was awarded $9,867 by a Los Angeles Superior Court small-claims commissioner after alleging that her 2006 Civic Hybrid did not meet mileage claims advertised by the manufacturer.[43]

text: Honda won an appeal against this decision when a judge ruled that the vehicle’s fuel-economy ratings complied with U.S. Environmental Protection Agency's requirements, and that such ratings are for the purpose of comparison among vehicles.[44]

text: Consumers who purchased or leased a 2003 through 2009 Honda Civic Hybrid had until April 19, 2013 to claim a cash payment and Rebate Certificate from the class action lawsuit settlement. However, the Settlement Administrator has already begun to review claims and began mailing checks last month to those with validated claims.

text: In March 2012 Honda Canada issued a release pledging to honor the USA class action settlement with owners and lessees in Canada when it was finalized in the USA. To date there has been no follow up to parties concerned, but shortly after the Honda release a class action was launched in Quebec courts on behalf of Quebec and Canadian owners and lessees.

text: Discontinuation[edit]

text: Honda announced that the Civic Hybrid will be discontinued after the 2015 model year due to poor sales along with the Honda Accord Plug-in Hybrid, Honda Civic GX, and Acura ILX Hybrid.


document_title: Connective tissue

question_text: what are the types of connective tissue proper

text: Connective tissue

text: Types[edit]

text: Connective tissue can be broadly subdivided into connective tissue proper, and special connective tissue.[5][6] Connective tissue proper consists of loose connective tissue and dense connective tissue (which is further subdivided into dense regular and dense irregular connective tissues.)[7] Loose and dense connective tissue are distinguished by the ratio of ground substance to fibrous tissue. Loose connective tissue has much more ground substance and a relative lack of fibrous tissue, while the reverse is true of dense connective tissue. Dense regular connective tissue, found in structures such as tendons and ligaments, is characterized by collagen fibers arranged in an orderly parallel fashion, giving it tensile strength in one direction. Dense irregular connective tissue provides strength in multiple directions by its dense bundles of fibers arranged in all directions.

text: Special connective tissue consists of reticular connective tissue, adipose tissue, cartilage, bone, and blood.[8] Other kinds of connective tissues include fibrous, elastic, and lymphoid connective tissues.[9] New vascularised connective tissue that forms in the process of wound healing is termed granulation tissue.[10] Fibroblasts are the cells responsible for the production of some CT.

text: Type I collagen is present in many forms of connective tissue, and makes up about 25% of the total protein content of the mammalian body.[11]

text: Characteristics[edit]

text: Characteristics of CT:

text:
Cells are spread through an extracellular fluid.
Ground substance - A clear, colorless, and viscous fluid containing glycosaminoglycans and proteoglycans to fix the body water and the collagen fibers in the intercellular spaces. Ground substance slows the spread of pathogens.
Fibers. Not all types of CT are fibrous. Examples of non-fibrous CT include adipose tissue and blood. Adipose tissue gives "mechanical cushioning" to the body, among other functions.[12][13] Although there is no dense collagen network in adipose tissue, groups of adipose cells are kept together by collagen fibers and collagen sheets in order to keep fat tissue under compression in place (for example, the sole of the foot). The matrix of blood is plasma.
Both the ground substance and proteins (fibers) create the matrix for CT. Connective tissues are derived from the mesenchyme.

text: Types of fibers:

text:
Tissue
Purpose
Components
Location

Collagenous fibers
Bind bones and other tissues to each other
Alpha polypeptide chains
tendon, ligament, skin, cornea, cartilage, bone, blood vessels, gut, and intervertebral disc.

Elastic fibers
Allow organs like arteries and lungs to recoil
Elastic microfibril and elastin
extracellular matrix

Reticular fibers
Form a scaffolding for other cells
Type III collagen
liver, bone marrow, and lymphatic organs

text: Function[edit]

text: Connective tissue has a wide variety of functions that depend on the types of cells and the different classes of fibers involved. Loose and dense irregular connective tissue, formed mainly by fibroblasts and collagen fibers, have an important role in providing a medium for oxygen and nutrients to diffuse from capillaries to cells, and carbon dioxide and waste substances to diffuse from cells back into circulation. They also allow organs to resist stretching and tearing forces. Dense regular connective tissue, which forms organized structures, is a major functional component of tendons, ligaments and aponeuroses, and is also found in highly specialized organs such as the cornea.[14]:161 Elastic fibers, made from elastin and fibrillin, also provide resistance to stretch forces.[14]:171 They are found in the walls of large blood vessels and in certain ligaments, particularly in the ligamenta flava.[14]:173

text: In hematopoietic and lymphatic tissues, reticular fibers made by reticular cells provide the stroma—or structural support—for the parenchyma—or functional part—of the organ.[14]:171

text: Mesenchyme is a type of connective tissue found in developing organs of embryos that is capable of differentiation into all types of mature connective tissue.[15] Another type of relatively undifferentiated connective tissue is mucous connective tissue, found inside the umbilical cord.[14]:160

text: Various types of specialized tissues and cells are classified under the spectrum of connective tissue, and are as diverse as brown and white adipose tissue, blood, cartilage and bone.[14]:158 Cells of the immune system, such as macrophages, mast cells, plasma cells and eosinophils are found scattered in loose connective tissue, providing the ground for starting inflammatory and immune responses upon the detection of antigens.[14]:161

text: Aging[edit]

text: Aging-related disorders in connective tissue-rich organs are common and cause major disabilities in the elderly. The production of mitochondrial reactive oxygen species appears to be a major determinant of aging (see Free radical theory of aging). Ordinarily mitochondrial superoxide dismutase (SOD2) protects against oxidative stress. Mutant mice with a connective tissue conditional deficiency for (SOD2) have an accelerated aging phenotype.[16] This aging phenotype includes weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis, muscle degeneration and reduced life span.

text: Clinical significance[edit]

text: There are many types of connective tissue disorders, such as:

text:
Connective tissue neoplasms including sarcomas such as hemangiopericytoma and malignant peripheral nerve sheath tumor in nervous tissue.
Congenital diseases include Marfan syndrome and Ehlers-Danlos Syndrome.
Myxomatous degeneration – a pathological weakening of connective tissue.
Mixed connective tissue disease – a disease of the autoimmune system, also undifferentiated connective tissue disease.
Systemic lupus erythematosus (SLE) – a major autoimmune disease of connective tissue
Scurvy, caused by a deficiency of vitamin C which is necessary for the synthesis of collagen.

text: Staining of connective tissue[edit]

text: For microscopic viewing, most of the connective tissue staining-techniques, colour tissue fibers in contrasting shades. Collagen may be differentially stained by any of the following:

text:
Van Gieson's stain
Masson's trichrome stain
Mallory's trichrome stain
Aniline blue stain
Eosin
Reticulin stain