Fukuda K, Higashida H, Kubo T, Maeda A, Akiba I, Bujo H, Mishina M, Numa S
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Nature. 1988 Sep 22;335(6188):355-8. doi: 10.1038/335355a0.
The primary structures of two muscarinic acetylcholine receptor (mAChR) species, designated as mAChR I and mAChR II, have been elucidated by cloning and sequence analysis of DNAs complementary to the porcine cerebral and cardiac messenger RNAs, respectively. mAChR I and mAChR II expressed in Xenopus oocytes differ from each other both in acetylcholine-induced response and in antagonist binding properties. These results, together with the differential tissue location of the two mAChR mRNAs, have indicated that pharmacologically distinguishable subtypes of the mAChR represent distinct gene products. The primary structures of two additional mammalian mAChR species, designated as mAChR III and mAChR IV, have subsequently been deduced from the nucleotide sequences of the cloned cDNAs or genomic DNAs. We report here that mAChR I and mAChR III expressed in NG108-15 neuroblastoma-glioma hybrid cells, but not mAChR II and mAChR IV, efficiently mediate phosphoinositide hydrolysis, activation of a Ca2+-dependent K+ current and inhibition of the M-current, a voltage-dependent K+ current sensitive to muscarinic agonists.
分别通过克隆和分析与猪脑和心脏信使核糖核酸互补的脱氧核糖核酸序列，阐明了两种毒蕈碱型乙酰胆碱受体（mAChR）亚型的一级结构，分别命名为mAChR I和mAChR II。在非洲爪蟾卵母细胞中表达的mAChR I和mAChR II在乙酰胆碱诱导的反应以及拮抗剂结合特性方面均存在差异。这些结果，连同两种mAChR信使核糖核酸在组织中的不同定位，表明mAChR在药理学上可区分的亚型代表不同的基因产物。随后，从克隆的互补脱氧核糖核酸或基因组脱氧核糖核酸的核苷酸序列中推导得出另外两种哺乳动物mAChR亚型的一级结构，分别命名为mAChR III和mAChR IV。我们在此报告，在NG108 - 15神经母细胞瘤 - 胶质瘤杂交细胞中表达的mAChR I和mAChR III，而非mAChR II和mAChR IV，能够有效地介导磷酸肌醇水解、激活钙依赖性钾电流以及抑制M电流（一种对毒蕈碱激动剂敏感的电压依赖性钾电流）。
