Muscarinic receptors and gastrointestinal tract smooth muscle function

Over the last decade, several lines of evidence have shown that both muscarinic M-2 and M-3 receptors are postjunctionally expressed in many smooth muscles, including the gastrointestinal tract. Although in vitro data suggests that both receptors are functional in that they inhibit adenylate cyclase activity and activate non-selective cation channels, few studies support a role in vivo. Thus, data from procedures that ablate the signaling pathway of the muscarinic M-2 receptor, including receptor antagonism, pertussis toxin pretreatment reveal little effect on gastrointestinal smooth muscle responsiveness to muscarinic agonists. Recently, information from knockout mice, lacking either M-2 or M-3 receptor, indicate reveal a role for both subtypes. However, the contribution of the M-2 receptor appears greater in the ileum than in the urinary bladder. Therapeutically, non-selective, as well as selective M-3 receptor antagonists are being clinically studied, although it remains to be shown which is the optimal approach to disorders of smooth muscle motility. (C) 2001 Elsevier Science Inc. All rights reserved.