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46 C 9 B Neurotransmitter
46 C 9 B Neurotransmitter
Postsynaptic
density
Voltage-
gated Ca++
channel
Synaptic
vesicle
Neurotransmitter
transporter
Receptor
Neurotransmitter
Axon terminal
Synaptic cleft
Dendrite
Contents
1 Mechanism
2 Discovery
3 Identification
4 Types
o 4.1 List of neurotransmitters, peptides, and gaseous signaling molecules
5 Actions
o 5.1 Excitatory and inhibitory
o 5.2 Examples of important neurotransmitter actions
6 Brain neurotransmitter systems
7 Drug effects
o 7.1 Agonists
o 7.2 Antagonists
7.2.1 Drug antagonists
o 7.3 Precursors
7.3.1 Catecholamine and trace amine precursors
7.3.2 Serotonin precursors
8 Diseases and disorders
9 Neurotransmitter imbalance
10 Elimination of neurotransmitters
11 See also
12 Notes
13 References
14 External links
Mechanism
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.
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.
Identification
However, given advances in pharmacology, genetics, and chemical neuroanatomy, the term
"neurotransmitter" can be applied to chemicals that:
Types
There are many different ways to classify neurotransmitters. Dividing them into amino acids,
peptides, and monoamines is sufficient for some classification purposes.
Major neurotransmitters:
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.
Single ions (such as synaptically released zinc) are also considered neurotransmitters by some, [12]
as well as some gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), and
hydrogen sulfide (H2S). 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.
The most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses
in the human brain.[6] 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.
Actions
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.
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
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.A brief comparison of these systems follows:
Nigrostriatal pathway
Tuberoinfundibular pathway
Arcuate nucleus →
Median eminence
Histaminergic pathways:
Tuberomammillary nucleus
(TMN) projections
TMN → Cerebral
cortex arousal (wakefulness)
Rostral projections
RN → Amygdala
RN → Cingulate
cortex
RN → Hippocampus
RN →
Hypothalamus
RN → Neocortex
RN → Septum
RN → Thalamus
RN → Ventral
tegmental area
Cholinergic pathways:
FCN →
Hippocampus
FCN → Cerebral arousal (wakefulness)
cortex emotion and mood
FCN → Limbic learning
Acetylcholine cortex and sensory motor function
system cortex motivation
(motivational salience)
Brainstem cholinergic nuclei
short-term memory
(BCN):
reward (minor role)
Pedunculopontine nucleus,
laterodorsal tegmentum, medial
habenula, and
parabigeminal nucleus
BCN → Ventral
tegmental area
BCN → Thalamus
.
Agonists
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)
Indirect agonists increase the binding of neurotransmitters at their target receptors by stimulating
the release or preventing the reuptake of neurotransmitters.[46] 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 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.
Antagonists
Main article: Receptor antagonist
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.
There are two main types of antagonist: direct-acting Antagonist and indirect-acting Antagonists:
1. 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.
2. Indirect-acting antagonist- drugs that inhibit the release/production of neurotransmitters
(e.g., Reserpine).
Drug antagonists
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".
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.
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
References
1.
Lodish, H.; Berk, A.; Zipursky, S.L. (2000). Molecular Cell Biology: Section
21.4Neurotransmitters, Synapses, and Impulse Transmission (4th ed.). New York: W. H.
Freeman.
Cherry, Kendra. "What is a Neurotransmitter?". Retrieved 6 October 2014.
"Neuropeptide database".
"Neuropeptides. IUPHAR/BPS Guide to pharmacology".
Elias, L. J, & Saucier, D. M. (2005). Neuropsychology: Clinical and Experimental
Foundations. Boston: Pearson
Robert Sapolsky (2005). "Biology and Human Behavior: The Neurological Origins of
Individuality, 2nd edition". The Teaching Company. see pages 13 & 14 of Guide Book
Saladin, Kenneth S. Anatomy and Physiology: The Unity of Form and Function. McGraw
Hill. 2009 ISBN 0-07-727620-5
"Junctions Between Cells". Retrieved 22 November 2010.