Autonomic effectors, cholinergic

Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the fact that muscarine does not have any therapeutic value, it is of interest because of its expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine, muscarine does not act on nicotinic receptors. 

It has been known for many years that autonomic effector tissues (eg, gut, airways, bladder) contain nerve fibers that do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Both motor and sensory NANC fibers are present. Although peptides are the most common transmitter substances found in these nerve endings, other substances, eg, nitric oxide synthase and purines, are also present in many nerve terminals (Table 6-1). Capsaicin, a neurotoxin derived from chili peppers, can cause the release of transmitter (especially substance P) from such neurons and, if given in high doses, destruction of the neuron. 

Actions of acetylcholine (ACh) are referred to as muscarinic based on the observation that muscarine acts selectively at certain sites and, quahtatively, produces the same effects as ACh. Peripheral muscarinic acetylcholine receptors are found primarily on autonomic effector cells innervated by postganghonic parasympathetic nerves and on some cells that receive little or no cholinergic innervation but express muscarinic receptors e.g., vascular endothelial cells). There are also muscarinic receptors in ganglia and the adrenal meduUa, where muscarinic stimulation seems to modulate the effects of nicotinic stimulation. Within the central nervous system (CNS), the hippocampus, cortex, and thalamus have high densities of muscarinic receptors. 

E. Nonadrenergic, Noncholinergic (NANC) Transmission Some nerve fibers in autonomic effector tissues do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Some of these are motor fibers that cause the release of ATP and possibly other purines related to it. Purine-evoked responses have been identified in the bronchi, gastrointestinal tract, and urinary tract. Other motor fibers are peptidergic, ie, they release peptides as the primary transmitters (see list above under Cotransmitters). 

The main acute pharmacologic actions of anti-ChE agents that are of concern here are those on the eye, the Intestine and ocher organs Innervated by the autonomic division of the FMS, the skeletal neuromuscular Junction, and the brain. Effects of cholinergic and adrenergic stimulation on effector organs are summarized in Table 1. 

Evidence that acetylcholine is a chemical mediator of synaptic transmission elsewhere in the central nervous system is circumstantial but convincing. Acetylcholine is the transmitter substance from motor nerves, preganglionic autonomic fibres and the postganglionic fibres of the parasympathetic system to their respective effector cells. In all these fibres, the activity of choline acetyltransferase (choline acetylase), the enzyme responsible for the synthesis of acetylcholine, is high. Conversely, its activity is negligibly low in sensory nerve fibres and transmission from these fibres is demonstrably non-cholinergic in nature . It is reasonable, therefore, to... 

The autonomic nervous system (ANS) consists of parasympathetic and sympathetic neurons. The transmitter for the parasympathetic system is acetylcholine (ACh), which acts on muscarinic and nicotinic cholinergic receptors. Muscarinic receptors are located on effector organs and mediate typical parasympathetic responses, such as. salivation, /acrimation, urination, and c/efecation (SLUD), as well as various cardiovascular responses. Prototypical muscarinic actions are ... 

Cholinergic transmission Acetylcholine (ACh) is the primary transmitter in all autonomic ganglia and at the parasympathetic postganglionic neuron-effector cell synapses. 

A. Organophosphorus (OP) compounds inhibit the enzyme acetylcholinesterase (AChE), allowing the accumulation of excessive acetylcholine at muscarinic receptors (cholinergic effector cells), at nicotinic receptors (skeletal neuromuscular junctions and autonomic ganglia), and in the central nervous system. 

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