FREE ESSAY ON NEURORANSMITTERS

NEURORANSMITTERS

Transmitter Molecule Derived From Site of Synthesis 
Acetylcholine Choline CNS, parasympathetic nerves 
Serotonin
5-Hydroxytryptamine (5-HT) Tryptophan CNS, chromaffin cells of the gut, enteric cells 
GABA Glutamate CNS 
Glutamate CNS 
Aspartate CNS 
Glycine spinal cord 
Histamine Histidine hypothalamus 
Epinephrine
synthesis pathway
Tyrosine adrenal medulla, some CNS cells 
Norpinephrine
synthesis pathway
Tyrosine CNS, sympathetic nerves 
Dopamine
synthesis pathway
Tyrosine CNS 
Adenosine ATP CNS, periperal nerves 
ATP sympathetic, sensory and enteric nerves 
Nitric oxide, NO Arginine CNS, gastrointestinal tract 
Many other neurotransmitters are derived from precursor proteins, the so-called peptide
neurotransmitters. As many as 50 different peptides have been shown to exert their
effects on neural cell function. Several of these peptide transmitters are derived from
the larger protein pre-opiomelanocortin (POMC). Neuropeptides are responsible for
mediating sensory and emotional responses including hunger, thirst, sex drive, pleasure
and pain. 
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Synaptic Transmission
Synaptic transmission refers to the propagation of nerve impulses from one nerve cell to
another. This occurs at a specialized cellular structure known as the synapse--- a
junction at which the axon of the presynaptic neuron terminates at some location upon the
postsynaptic neuron. The end of a presynaptic axon, where it is juxtaposed to the
postsynaptic neuron, is enlarged and forms a structure known as the terminal button. An
axon can make contact anywhere along the second neuron: on the dendrites (an axodendritic
synapse), the cell body (an axosomatic synapse) or the axons (an axo-axonal synapse). 
Nerve impulses are transmitted at synapses by the release of chemicals called
neurotransmitters. As a nerve impulse, or action potential, reaches the end of a
presynaptic axon, molecules of neurotransmitter are released into the synaptic space. The
neurotransmitters are a diverse group of chemical compounds ranging from simple amines
such as dopamine and amino acids such as g-aminobutyrate (GABA), to polypeptides such as
the enkephalins. The mechanisms by which they elicit responses in both presynaptic and
postsynaptic neurons are as diverse as the mechanisms employed by growth factor and
cytokine receptors. 
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Neuromuscular Transmission
A different type of nerve transmission occurs when an axon terminates on a skeletal
muscle fiber, at a specialized structure called the neuromuscular junction. An action
potential occurring at this site is known as neuromuscular transmission. At a
neuromuscular junction, the axon subdivides into numerous terminal buttons that reside
within depressions formed in the motor end-plate. The particular transmitter in use at
the neuromuscular junction is acetylcholine. 
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Neurotransmitter Receptors
Once the molecules of neurotransmitter are released from a cell as the result of the
firing of an action potential, they bind to specific receptors on the surface of the
postsynaptic cell. In all cases in which these receptors have been cloned and
characterized in detail, it has been shown that there are numerous subtypes of receptor
for any given neurotransmitter. As well as being present on the surfaces of postsynaptic
neurons, neurotransmitter receptors are found on presynaptic neurons. In general,
presynaptic neuron receptors act to inhibit further release of neurotransmitter. 
The vast majority of neurotransmitter receptors belong to a class of proteins known as
the serpentine receptors. This class exhibits a characteristic transmembrane structure:
that is, it spans the cell membrane, not once but seven times. The link between
neurotransmitters and intracellular signaling is carried out by association either with
G-proteins (small GTP-binding and hydrolyzing proteins) or with protein kinases, or by
the receptor itself in the form of a ligand-gated ion channel (for example, the
acetylcholine receptor). One additional characteristic of neurotransmitter receptors is
that they are subject to ligand-induced desensitization: That is, they can become
unresponsive upon prolonged exposure to their neurotransmitter. 
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Acetylcholine
Acetylcholine (ACh) is a simple molecule synthesized from choline and acetyl-CoA through
the action of choline acetyltransferase. Neurons that synthesize and release ACh are
termed cholinergic neurons. When an action potential reaches the terminal button of a
presynaptic neuron a voltage-gated calcium channel is opened. The influx of calcium ions,
Ca2+, stimulates the exocytosis of presynaptic vesicles containing ACh, which is thereby
released into the synaptic cleft. Once released, ACh must be removed rapidly in order to
allow repolarization to take place; this step, hydrolysis, is carried out by the enzyme,
acetylcholinesterase. The acetylcholinesterase found at nerve endings is anchored to the
plasma membrane through a glycolipid. 
ACh receptors are ligand-gated cation channels composed of four different polypeptide
subunits arranged in the form [(a2)(b)(g)(d)]. Two main classes of ACh receptors have
been identified on the basis of their responsiveness to the toadstool alkaloid,
muscarine, and to nicotine, respectively: the muscarinic receptors and the nicotinic
receptors. Both receptor classes are abundant in the human brain. Nicotinic receptors are
further divided into those found at neuromuscular junctions and those found at neuronal
synapses. The activation of ACh receptors by the binding of ACh leads to an influx of Na+
into the celland an efflux of K+, resulting in a depolarization of the postsynaptic
neuron and the initiation of a new action potential. 
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Cholinergic Agonists and Antagonists
Numerous compounds have been identified that act as either agonists or antagonists of
cholinergic neurons. The principal action of cholinergic agonists is the excitation or
inhibition of autonomic effector cells that are innervated by postganglionic
parasympathetic neurons and as such are refered to as parasympathomimetic agents. The
cholinergic agonists include choline esters (such as ACh itself) as well as protein- or
alkaloid-based compounds. Several naturally occurring compounds have been shown to affect
cholinergic nerons, either positively or negatively. 
The responses of cholinergic neurons can also be enhanced by administration of
cholinesterase (ChE) inhibitors. ChE inhibitors have been used as components of nerve
gases but also have significant medical application in the treatment of disorders such as
glaucoma and myasthenia gravis as well as in terminating the effects of neuromuscular
blocking agents such as atropine. 
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Natural Cholinergic Agonist and Antagonists
Source of Compound Mode of Action 
Agonists 
Nicotine Alkaloid prevalent in the tobacco plant Activates nicotinic class of ACh
receptors, locks the channel open 
Muscarine Alkaloid produced by Amanita muscaria mushrooms Activates muscarinic class of
ACh receptors 
a-Latrotoxin