Two Main Classes Of Ach Receptors example essay topic

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 Norepinephrine synthesis pathway Tyrosine CNS, sympathetic nerves Dopamine synthesis pathway Tyrosine CNS Adenosine ATP CNS, peripheral 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 (POM C). Neuropeptides are responsible for mediating sensory and emotional responses including hunger, thirst, sex drive, pleasure and pain. back to the top 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 axo dendritic synapse), the cell body (an axo somatic synapse) or the axons (an axo-axonal synapse). Nerv 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-amino butyrate (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. back to the top 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. back to the top 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. back to the top 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, Ca 2+, 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 re polarization 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 [ (a 2) (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 cell and an efflux of K+, resulting in a depolarization of the postsynaptic neuron and the initiation of a new action potential. back to the top 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 post ganglionic 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 neurons, 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. 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 mus caria mushrooms Activates muscarinic class of ACh receptors a-Latrotoxin.