Acetylcholine cholinergic nervous system

Acetylcholine receptors have been classified into sub-types based on early studies of pharmacologic selectivity. Long before structures were known, two crude alkaloid fractions, containing nicotine and muscarine (Fig. 11-2), were used to subclassify receptors in the cholinergic nervous system (Fig. 11-3). The greatly different... 

Holte, HR., Eriksen, S., Skulberg, O., and Aas, P 1998. The effect of water soluble cyanotoxin(s) produced by two species of Anabaena on the release of acetylcholine from the peripheral cholinergic nervous system of the rat airway. Environ Toxicol Pharmacol 5, 51-59. 

The transmission of impulses throughout the cholinergic nervous system is mediated by acetylcholine (1), and compounds that produce... 

Dominating signs of poisoning with OP and nerve agents are caused by hyperstimulation of the cholinergic nervous system due to an elevated level of acetylcholine caused by inhibition of AChE (acute cholinergic crisis). 

The cholinergic nervous system is a network of neurones spread through both the central and peripheral nervous systems which are characterised by synapses. Transmission of signals within the network is electrical except at the synapses where acetylcholine (ACh) is released to carry the impulses across a small gap to the next neurone or to an effector organ. It is ACh which gives the cholinergic nervous system its name. ACh is only one of the many chemical transmitters in the nervous system, whose function is to act as amplifying relay stations for the nerve impulses from the brain. 

Cholinergic Transmission is the process of synaptic transmission which uses mainly acetylcholine as a transmitter. Cholinergic transmission is found widely in the peripheral and central nervous system, where acetylcholine acts on nicotinic and muscarinic receptors. 

Acetylcholinesterase is a component of the postsynaptic membrane of cholinergic synapses of the nervous system in both vertebrates and invertebrates. Its structure and function has been described in Chapter 10, Section 10.2.4. Its essential role in the postsynaptic membrane is hydrolysis of the neurotransmitter acetylcholine in order to terminate the stimulation of nicotinic and muscarinic receptors (Figure 16.2). Thus, inhibitors of the enzyme cause a buildup of acetylcholine in the synaptic cleft and consequent overstimulation of the receptors, leading to depolarization of the postsynaptic membrane and synaptic block. 

The development of antibodies against ChAT allowed the distribution of neurons producing acetylcholine in the nervous system to be revealed (Mesulam et al., 1983 Armstrong et al., 1983 Jones Beaudet, 1987 Vincent Reiner, 1987). In the context of control of wakefulness and REM sleep two groups of cholinergic neurons are of primary importance. Neurons located in the basal forebrain and medial septum provide the cholinergic innervation of the cerebral... 

Adrenaline (epinephrine)-producing (adrenergic) and acetylcholine secreting (cholinergic) neurones of the autonomic nervous system have direct and complimentary effects on the tone of blood vessels. 

Perhaps the most prominent and well-studied class of synthetic poisons are so-called cholinesterase inhibitors. Cholinesterases are important enzymes that act on compounds involved in nerve impulse transmission - the neurotransmitters (see the later section on neurotoxicity for more details). A compound called acetylcholine is one such neurotransmitter, and its concentration at certain junctions in the nervous system, and between the nervous system and the muscles, is controlled by the enzyme acetylcholinesterase the enzyme causes its conversion, by hydrolysis, to inactive products. Any chemical that can interact with acetylcholinesterase and inhibit its enzymatic activity can cause the level of acetylcholine at these critical junctions to increase, and lead to excessive neurological stimulation at these cholinergic junctions. Typical early symptoms of cholinergic poisoning are bradycardia (slowing of heart rate), diarrhea, excessive urination, lacrimation, and salivation (all symptoms of an effect on the parasympathetic nervous system). When overstimulation occurs at the so-called neuromuscular junctions the results are tremors and, at sufficiently high doses, paralysis and death. 

The cholinesterases, acetylcholinesterase and butyrylcholinesterase, are serine hydrolase enzymes. The biological role of acetylcholinesterase (AChE, EC 3.1.1.7) is to hydrolyze the neurotransmitter acetylcholine (ACh) to acetate and choline (Scheme 6.1). This plays a role in impulse termination of transmissions at cholinergic synapses within the nervous system (Fig. 6.7) [12,13]. Butyrylcholinesterase (BChE, EC 3.1.1.8), on the other hand, has yet not been ascribed a function. It tolerates a large variety of esters and is more active with butyryl and propio-nyl choline than with acetyl choline [14]. Structure-activity relationship studies have shown that different steric restrictions in the acyl pockets of AChE and BChE cause the difference in their specificity with respect to the acyl moiety of the substrate [15]. AChE hydrolyzes ACh at a very high rate. The maximal rate for hydrolysis of ACh and its thio analog acetyl-thiocholine are around 10 M s , approaching the diffusion-controlled limit [16]. 

Acetylcholine is the primary neurotransmitter in the parasympathetic division of the autonomic nervous system, which mainly innervates the gastrointestinal tract, eyes, heart, respiratory tract, and secretory glands. Although its receptors are crucial for maintaining all normal functions of the body, an extremely small number of illnesses can be explained by the dysfunction of cholinergic regions of the peripheral autonomic system. 

There is considerable diversity among nicotinic acetylcholine receptors, and at least one source of this diversity is the multiplicity of acetylcholine receptor genes. Cholinergic-nicotinic receptors in skeletal muscle are different from those in autonomic ganglia and the central nervous system. 

The parasympathetic nervous system, through the vagus nerve, inhibits the spontaneous rate of depolarization of pacemaker cells. The release of acetylcholine from cholinergic vagal fibers increases potassium conductance (gK+) in pacemaker cells, and this enhanced outward movement of K+ results in a more negative po-... 

Mecfianism of Action A cholinergic-receptor agonist that binds to acetylcholine receptors, producing both stimulating and depressant effects on the peripheral and central nervous systems. Therapeutic Effect Provides a source of nicotine during nicotine withdrawal and reduces withdrawal symptoms. 

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