Muscarinic receptors and gastrointestinal tract smooth muscle function.
Over the last decade, several lines of evidence have shown that both muscarinic M2 and M3 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 M2 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 M2 or M3 receptor, indicate reveal a role for both subtypes. However, the contribution of the M2 receptor appears greater in the ileum than in the urinary bladder. Therapeutically, non-selective, as well as selective M3 receptor antagonists are being clinically studied, although it remains to be shown which is the optimal approach to disorders of smooth muscle motility.
Eglen
R M
RM
DiscoveRx Corp, Fremont, CA 94538, USA. reglen@discoverx.com
D000818:Animals; D003109:Colonic Diseases, Functional / Q000188:drug therapy; D004064:Digestive System / Q000033:anatomy & histology; D004068:Digestive System Physiological Phenomena; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000502:physiology* / Q000503:physiopathology; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000188:drug therapy
D007473:Ion Channels; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic