Nerve function acetylcholine

Acetylcholine is a neurotransmitter that functions at the neuromuscular junction, carrying signals from the nerve to the muscle. It is synthesized in a reaction between the quaternary ammonium ion choline and acetyl coenzyme A (Figure 16.10). When it is released from the nerve cell, acetylcholine binds to receptors on the surface of muscle cells. This binding stimulates the muscle cell to contract. Acetylcholine is then broken down to choline and acetate ion. 

D. Antiacetylcholinesterase Neurotoxins. The fourth type of neurotoxin is the one that binds to acetylcholinesterase (Rodriquez-Ithurralde et al., 1981 Cervenansky et al., 1991). When acetylcholinesterase is not functioning, acetylcholine (after binding to the acetylcholine receptor) cannot be hydrolyzed consequently, normal nerve transmission is impaired. Acetylcholinesterase action of D. angusticeps venom was first reported by Ro-driguez-Ithurralde et al. (1983). 

Choline functions in fat metaboHsm and transmethylation reactions. Acetylcholine functions as a neurotransmitter in certain portions of the nervous system. Acetylcholine is released by a stimulated nerve cell into the synapse and binds to the receptor site on the next nerve cell, causing propagation of the nerve impulse. 

While these functions can be a carried out by a single transporter isoform (e.g., the serotonin transporter, SERT) they may be split into separate processes carried out by distinct transporter subtypes, or in the case of acetylcholine, by a degrading enzyme. Termination of cholinergic neurotransmission is due to acetylcholinesterase which hydrolyses the ester bond to release choline and acetic acid. Reuptake of choline into the nerve cell is afforded by a high affinity transporter (CHT of the SLC5 gene family). 

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

It is already evident that the turnover rate of a transmitter is only a crude measure of its release rate. Further limitations are that there is appreciable intraneuronal metabolism of some neurotransmitters notably, the monoamines. In such cases, turnover will overestimate release rate. Another problem, again affecting monoamines, is that some of the released neurotransmitter is taken back into the nerve terminals and recycled. This leads to an underestimate of release rate. Despite these drawbacks, studies of turnover rates uncovered some important features of transmitter release. In particular, they provided the first evidence for distinct functional pools of monoamines, acetylcholine and possibly other neurotransmitters a release pool, which could be rapidly mobilised for release, and a storage or reserve pool which had a slower turnover rate. 

Enteric nerves control intestinal smooth muscle action and are connected to the brain by the autonomic nervous system. IBS is thought to result from dysregulation of this brain-gut axis. The enteric nervous system is composed of two gan-glionated plexuses that control gut innervation the submucous plexus (Meissner s plexus) and the myenteric plexus (Auerbach s plexus). The enteric nervous system and the central nervous system (CNS) are interconnected and interdependent. A number of neurochemicals mediate their function, including serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P, and nitric oxide, among others. 

Both the G- and V-agents have the same physiological action on humans. They are potent inhibitors of the enzyme acetylcholinesterase (AChE), which is required for the function of many nerves and muscles in nearly every multicellular animal. Normally, AChE prevents the accumulation of acetylcholine after its release in the nervous system. Acetylcholine plays a vital role in stimulating voluntary muscles and nerve endings of the autonomic nervous system and many structures within the CNS. Thus, nerve agents that are cholinesterase inhibitors permit acetylcholine to accumulate at those sites, mimicking the effects of a massive release of acetylcholine. The major effects will be on skeletal muscles, parasympathetic end organs, and the CNS. 

Lindstrom, J.M. Nicotinic acetylcholine receptors of muscles and nerves comparison of their structures, functional roles, and vulnerability to pathology. Ann. N.Y. Acad. Sci. 998 41, 2003. 

Sanders-. But the nerves can still be stimulated and they still release acetylcholine, so they are not non-functional. 

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