Lechleiter J, Peralta E, Clapham D
Trends Pharmacol Sci. 1989 Dec;Suppl:34-8.
Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensitive G proteins. Additionally, the cardiac M2 receptor is closely coupled to a K+ current (IK.ACh). To characterize this functional diversity more completely, we measured the ACh-induced Ca2+ responses of cells transfected with the muscarinic receptor subtypes m1, m2, m3 and m4. As expected, cells transfected with m1 or m3 receptors exhibited large dose-dependent increases in Ca2+ in response to ACh application. Unexpectedly, cells transfected with m2 or m4 receptors also exhibited increases in Ca2+ in response to agonist application. The m2- or m4-coupled responses were smaller in amplitude, required higher concentrations of agonist and were much more sensitive to PTX treatment when compared to m1- or m3-coupled responses. We discuss this remarkable diversity of function in terms of the receptor subtype's coupling to G proteins.
毒蕈碱型乙酰胆碱受体亚型m1、m3和m5与磷脂酰肌醇代谢密切相关，因此通过对百日咳毒素（PTX）敏感和不敏感的G蛋白与细胞内Ca2+浓度相关。毒蕈碱受体亚型m2和m4通过对PTX敏感的G蛋白强烈抑制腺苷酸环化酶的产生。此外，心脏M2受体与钾电流（IK.ACh）密切相关。为了更全面地表征这种功能多样性，我们测量了转染有毒蕈碱受体亚型m1、m2、m3和m4的细胞对乙酰胆碱诱导的Ca2+反应。正如预期的那样，转染有m1或m3受体的细胞在应用乙酰胆碱后表现出剂量依赖性的Ca2+大幅增加。出乎意料的是，转染有m2或m4受体的细胞在应用激动剂后也表现出Ca2+增加。与m1或m3偶联的反应相比，m2或m4偶联的反应幅度较小，需要更高浓度的激动剂，并且对PTX处理更为敏感。我们从受体亚型与G蛋白的偶联角度讨论了这种显著的功能多样性。
