Acetylcholine receptors classification

Caulfield MP, Birdsall NJM (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50 279-290... 

Caulfield, M. P. Birdsall, N. J. (1998). International union of pharmacology. XVIII. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev. 50, 279-90. 

As given in classification, these agents are of two type e.g. reversible and irreversible. The reversible anticholinesterases have a structural resemblance to acetylcholine, are capable of combining with anionic and esteratic sites of cholinesterase as well as with acetylcholine receptor. The complex formed with the esteratic site of cholinesterase is less readily hydrolyzed than the acetyl esteratic site complex formed with acetylcholine. Edrophonium forms reversible complex with the anionic site and has shorter duration of action. Also, neostigmine and edrophonium have a direct stimulating action at cholinergic sites. 

FIGURE 18-2 Receptor classifications and subclassifications for acetylcholine (ACh] and norepinephrine [NE], the two primary neurotransmitters used in the autonomic nervous system. 

Caulfield MP, Birdsall NJ (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50 279-90 Caulfield MP, Robbins J, Higashida H, Brown DA (1993) Postsynaptic actions of acetyl-choline the coupling of muscarinic receptor subtypes to neuronal ion channels. Progr Brain... 

Nicotine served as an experimental tool for the classification of acetylcholine receptors. 

Neither nicotine nor muscarine is a normal physiological component of the mammalian body hence the muscarinic/nicotinic classification of acetylcholine receptors is artificial. Although it is well established that muscarine... 

Nicotine mimics acetylcholine at sites (a) and (b), whereas muscarine does so at site (c) (see Table 7.1). Hence it is usual to divide acetylcholine receptors into nicotinic and muscarinic receptors, a useful classification first made by Dale (1914). The work of muscarinic and nicotinic receptors is carried out on very different time scales. A single nervous stimulus affects muscarinic receptors for at least 500 ms, a long duration that is preceded by a latency of about 100 ms. In contrast to this, nicotinic receptors at voluntary neuromuscular junctions are stimulated for only 0.2 ms, and even the ganglionic synapses, which are slower, average only 60 ms. Cyclic GMP is thought to be a necessary mediator of muscarinic reponses. One consequence of interest is that smooth muscle reacts far more slowly than voluntary muscle. Heart muscle is distinguished from both by the fact that acetylcholine increases its polarization (and hence slows the heart), whereas it decreases polarization in other types of muscle. 

Nicotine mimics acetylcholine at sites (a) and (b), whereas muscarine does so at site (c) (see Table 7.1). Hence it is usual to divide acetylcholine receptors into nicotinic and muscarinic receptors, a useful classification first made by Dale (1914). The work of muscarinic and nicotinic receptors... 

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

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. 

Since there are two primary neurotransmitters involved in autonomic discharge, there are two primary classifications of postsynaptic receptors. Cholinergic receptors are located at acetylcholine synapses, and adrenergic receptors are located at norepinephrine synapses. As indicated in Figure 18-2, each type of receptor has several subclassifications. The location and functional significance of these classifications and subclassifications are presented here. 

Dopamine induces biochemical and physiological effects in the mammalian neostriatum. The occurrence of a D-l dopamine receptor (in the classification scheme of Kebabian and Caine) accounts for the ability of dopamine to enhance cyclic AMP formation. The occurrence of a D-2 dopamine receptor accounts for the ability of dopamine to inhibit cyclic AMP formation brought about by stimulation of a D-l dopamine receptor. Dopamine receptors mediate the regulation of (1) the release or turnover of acetylcholine (postsynaptic dopamine receptor) and (2) the release or turnover of dopar mine (presynaptic autoreceptor). Both receptors can be classified as D-2 dopamine receptors. Indications for the occurrence of dopamine receptors affecting the release or turnover of GABA, glutamate, serotonin and several neuropeptides are evaluated. 

The concept that muscarinic and nicotinic receptors may explain the different physiologic responses produced by acetylcholine viras derived from this early research of Dale and Loeviri. Although it currently is recognized that there are multiple subclasses of both muscarinic and nicotinic receptors, the general classification of these tvtro types of cholinergic receptors continues to... 

Loewi went on to characterise the synapses of the autonomic nervous system as nicotinic or muscarinic (where acetylcholine mimics the action of nicotine or muscarine when directly applied to the S3mapse). This classification exists to the present day and has been developed to include subclasses of receptor. 

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