Ashkenazi A, Winslow J W, Peralta E G, Peterson G L, Schimerlik M I, Capon D J, Ramachandran J
Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.
Science. 1987 Oct 30;238(4827):672-5. doi: 10.1126/science.2823384.
To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was significantly less efficient and more dependent on receptor levels than the inhibition of adenylyl cyclase. Both responses were mediated by guanine nucleotide binding proteins, as evidenced by their inhibition by pertussis toxin; the more efficiently coupled adenylyl cyclase response was significantly more sensitive. Thus, individual subtypes of a given receptor are capable of regulating multiple effector pathways.
为了研究特定受体亚型是否能与多种效应系统偶联，在缺乏内源性受体的细胞中表达了重组M2毒蕈碱受体。毒蕈碱激动剂卡巴胆碱既抑制腺苷酸环化酶又刺激磷酸肌醇水解。与腺苷酸环化酶的抑制相比，磷酸肌醇水解的刺激效率明显较低，且更依赖于受体水平。两种反应均由鸟嘌呤核苷酸结合蛋白介导，百日咳毒素对它们的抑制作用证明了这一点；偶联效率更高的腺苷酸环化酶反应明显更敏感。因此，给定受体的各个亚型能够调节多种效应途径。
