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Muscarinic Receptor Subtypes in the Lower Urinary Tract.

Review article
Authors Daniel Giglio
Gunnar Tobin
Published in Pharmacology
Volume 83
Issue 5
Pages 259-269
ISSN 1423-0313
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 259-269
Language en
Links dx.doi.org/10.1159/000209255
Subject categories Pharmacology

Abstract

Acetylcholine acting on muscarinic M(3) receptors on the detrusor muscle is the principal stimulus for inducing the contractile response for urinary bladder voiding. The urinary bladder expresses, however, all cloned muscarinic receptor subtypes (M(1)-M(5)). In terms of quantity, the M(2) subtype dominates over the M(3) subtype in the detrusor, and its role in contraction seems to be primarily indirect, by blocking stimuli from cAMP-coupled receptors that induce relaxation. The excitatory M(1) and inhibitory M(2) and/or M(4) subtypes are also expressed prejunctionally. Muscarinic M(1) and M(2)/M(4) autoreceptors facilitate and inhibit, respectively, the release of acetylcholine. The urothelium had been considered to be a passive barrier; however, during the last decade, it has been shown that the urothelium is of importance for bladder function. In a state of bladder pathology, muscarinic receptor changes occur in the detrusor, prejunctionally, and in the urothelium, but the character of the change differs between disorders. The urothelium expresses all subtypes of muscarinic receptors, and upon stimulation it releases factors affecting bladder afferents and smooth muscle. During inflammation, the expression of muscarinic M(5) receptors is increased, particularly in the urothelium, together with a cholinergic-induced production of nitric oxide in the mucosa. The present review describes signalling mechanisms, expression and functional effects of muscarinic receptors in the lower urinary tract. Their roles in physiological and pathophysiological conditions, as well as clinical implications of the occurrence of different muscarinic receptors, are discussed.

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