Muscarinic agonists and antagonists: effects on gastrointestinal function.
Muscarinic agonists and antagonists: effects on gastrointestinal function.
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DOI：
10.1007/978-3-642-23274-9_15
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Griffin, Michael T
中科院分区：
文献类型：
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作者：
Ehlert, Frederick J;Pak, Kirk J;Griffin, Michael T
M受体激动剂和拮抗剂用于治疗少数胃肠道(GI)疾病，这些疾病与唾液分泌受损或胃肠道平滑肌动力改变有关。在外分泌方面，在唾液、胃和胰腺中表达的主要M受体是M₃，M₁受体的贡献很小。在胃肠道平滑肌中，M₂和M₃是主要的M受体，M₂与M₃的数量之比至少为4：1。平滑肌收缩和外分泌的拮抗作用通常与M-₃受体机制相一致，尽管M-₂受体主要存在于平滑肌中。这些结果与M₂受体在平滑肌中的条件性作用是一致的。也就是说，M₂受体的收缩作用依赖于M₃的收缩作用，因此M₃受体的拮抗作用消除了M₂的反应。M受体在胃肠道中的生理作用与其已知的信号机制是一致的。一些所谓的组织选择性M-₃拮抗剂可能将它们的选择性归功于与非M受体靶点的高度有效的相互作用。
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.