Ehlert Frederick J, Pak Kirk J, Griffin Michael T
Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
Handb Exp Pharmacol. 2012(208):343-74. doi: 10.1007/978-3-642-23274-9_15.
Muscarinic agonists and antagonists are used to treat a handful of gastrointestinal (GI) conditions associated with impaired salivary secretion or altered motility of GI smooth muscle. With regard to exocrine secretion, the major muscarinic receptor expressed in salivary, gastric, and pancreatic glands is the M₃ with a small contribution of the M₁ receptor. In GI smooth muscle, the major muscarinic receptors expressed are the M₂ and M₃ with the M₂ outnumbering the M₃ by a ratio of at least four to one. The antagonism of both smooth muscle contraction and exocrine secretion is usually consistent with an M₃ receptor mechanism despite the major presence of the M₂ receptor in smooth muscle. These results are consistent with the conditional role of the M₂ receptor in smooth muscle. That is, the contractile role of the M₂ receptor depends on that of the M₃ so that antagonism of the M₃ receptor eliminates the response of the M₂. The physiological roles of muscarinic receptors in the GI tract are consistent with their known signaling mechanisms. Some so-called tissue-selective M₃ antagonists may owe their selectivity to a highly potent interaction with a nonmuscarinic receptor target.
毒蕈碱激动剂和拮抗剂用于治疗一些与唾液分泌受损或胃肠道平滑肌运动改变相关的胃肠道疾病。关于外分泌，唾液腺、胃腺和胰腺中表达的主要毒蕈碱受体是M₃，M₁受体的贡献较小。在胃肠道平滑肌中，表达的主要毒蕈碱受体是M₂和M₃，其中M₂的数量比M₃至少多四倍。尽管平滑肌中主要存在M₂受体，但平滑肌收缩和外分泌的拮抗作用通常与M₃受体机制一致。这些结果与M₂受体在平滑肌中的条件性作用一致。也就是说，M₂受体的收缩作用取决于M₃的作用，因此M₃受体的拮抗作用消除了M₂的反应。毒蕈碱受体在胃肠道中的生理作用与其已知的信号传导机制一致。一些所谓的组织选择性M₃拮抗剂的选择性可能归因于与非毒蕈碱受体靶点的高效相互作用。
