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Neurotransmitter
From Wikipedia, the free encyclopedia
Neurotransmitters are chemicals that are used to relay, amplify and modulate signals between a neuron and another cell. According to the prevailing beliefs of the 1960s, a chemical can be classified as a neurotransmitter if it meets the following conditions:
- There are precursors and/or synthesis enzymes located in the presynaptic neuron;
- The chemical must be present in the presynaptic element
- It is available in sufficient quantity in the presynaptic neuron to affect the postsynaptic neuron;
- There must be postsynaptic receptors and the ability for the chemical to bind to said receptors
- A biochemical mechanism for inactivation must be present.
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There are many different ways to classify neurotransmitters. Often, dividing them into amino acids, peptides, and monoamines is sufficient for many purposes.
Some more precise divisions are as follows:
- Around 10 "small-molecule neurotransmitters" are known:
- acetylcholine
- monoamines (epinephrine E, norepinephrine NE, dopamine DA, serotonin 5-HT, and melatonin)
- 3 or 4 amino acids, depending on exact definition used: (primarily glutamic acid, GABA, aspartic acid & glycine)
- Purines, (Adenosine, ATP, GTP and their derivatives)
- Fatty acids are also receiving attention as the potential endogenous cannabinoid.[citation needed]
- Over 50 neuroactive peptides (vasopressin, somatostatin, neurotensin, etc.) have been found, among them hormones such as LH or insulin that have specific local actions in addition to their long-range signalling properties.
- Single ions, such as synaptically-released zinc, are also considered neurotransmitters by some.[citation needed]
- Nitrogen monoxide (NO)
The major "workhorse" neurotransmitters of the brain are glutamic acid (=glutamate) and GABA.
Some examples of neurotransmitter action:
- Acetylcholine - voluntary movement of the muscles
- Norepinephrine - wakefulness or arousal
- Dopamine - voluntary movement and motivation, "wanting", pleasure, associated with addiction and love
- Serotonin - memory, emotions, wakefulness, sleep and temperature regulation
- GABA (gamma aminobutyric acid) - inhibition of motor neurons
- Glycine - spinal reflexes and motor behaviour
- Neuromodulators - sensory transmission-especially pain
It is important to appreciate that it is the receptor that dictates the neurotransmitter's effect.
Within the cells, small-molecule neurotransmitters are usually packaged in synaptic vesicles. When an action potential reaches the cell body, the rapid depolarization causes calcium ion (Ca2) channels to open. Calcium then stimulates the transport of vesicles to the synaptic membrane and their release at synaptic buttons - a form of exocytosis. These neurotransmitters are released in quanta, whereby a single quantum consists of a vesicle containing possibly thousands of neurotransmitters[1].
The neurotransmitters then diffuse across the synaptic cleft to bind to densely and geometrically arranged receptors. The receptors are broadly classified into ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated ion channels that open or close through neurotransmitter binding. Metabotropic receptors, which can have a diverse range of effects on a cell, transduct the signal by secondary messenger systems, or G-proteins.
Neuroactive peptides are made in the neuron's soma and are transported through the axon to the synapse. They are usually packaged into dense-core vesicles and are released through a similar, but metabolically distinct, form of exocytosis used for small-molecule synaptic vesicles.
Some neurotransmitter/neuromodulators like zinc not only can modulate the sensitivity of a receptor to other neurotransmitters (allosteric modulation) but can even penetrate specific, gated channels in post-synaptic neurons, thus entering the post-synaptic cells. This "translocation" is another mechanism by which synaptic transmitters can affect postsynaptic cells.
A neurotransmitter's effect is determined by its receptor. For example, GABA can act on both rapid or slow inhibitory receptors (the GABA-A and GABA-B receptor respectively). Many other neurotransmitters, however, may have excitatory or inhibitory actions depending on which receptor they bind to.
Neurotransmitters may cause either excitatory or inhibitory post-synaptic potentials. That is, they may help the initiation of a nerve impulse in the receiving neuron, or they may discourage such an impulse by modifying the local membrane voltage potential. In the central nervous system, combined input from several synapses is usually required to trigger an action potential. Glutamate is the most prominent of excitatory transmitters; GABA and glycine are well-known inhibitory neurotransmitters.
Many neurotransmitters are removed from the synaptic cleft by neurotransmitter transporters in a process called reuptake (or often simply 'uptake'). Without reuptake, the molecules might continue to stimulate or inhibit the firing of the postsynaptic neuron. Another mechanism for removal of a neurotransmitter is digestion by an enzyme. For example, at cholinergic synapses (where acetylcholine is the neurotransmitter), the enzyme acetylcholinesterase breaks down the acetylcholine. Neuroactive peptides are often removed from the cleft by diffusion, and eventually broken down by proteases.
Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system causes effects in large volumes of the brain, called volume transmission.
The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system.
Drugs targetting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs;
- Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
- Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the effect of naturally released serotonin.
- 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.
Diseases may affect specific neurotransmitter systems. For example, Parkinson's disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.
A brief comparison of the major neurotransmitter systems follows:
| System | Origin [2] | Effects[2] |
|---|---|---|
| Noradrenaline system | locus coeruleus |
|
| Lateral tegmental field | ||
| Dopamine system | dopamine pathways: | motor system, reward, cognition, endocrine, nausea |
| Serotonin system | caudal dorsal raphe nucleus | Increase (introverson), mood, satiety, body temperature and sleep, while decreasing nociception. |
| rostral dorsal raphe nucleus | ||
| Cholinergic system | pontomesencephalotegmental complex |
|
| basal optic nucleus of Meynert | ||
| medial septal nucleus |
- ^ J. Del Castillo and B. Katz, "The effect of magnesium on the activity of motor nerve endings", 124:553-559
- ^ a b Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone, page 474 for noradrenaline system, page 476 for dopamine system, page 480 for serotonin system and page 483 for cholinergic system.. ISBN 0-443-07145-4.
- Molecular Expressions Photo Gallery: The Neurotransmitter Collection
- Brain Neurotransmitters
- Endogenous Neuroactive Extracellular Signal Transducers
- MeSH Neurotransmitter
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| Key concepts | Ligand - Cell signaling networks - Signal transduction - Apoptosis - Second messenger system (Ca2+ signaling, Lipid signaling) |
| Processes | Paracrine - Autocrine - Juxtacrine - Neurotransmitters - Endocrine (Neuroendocrine) |
| Types of proteins | Receptor (Transmembrane, Intracellular) - Transcription factor (General, Preinitiation complex, TFIID, TFIIH) - Adaptor protein |