Levy F O, Gudermann T, Perez-Reyes E, Birnbaumer M, Kaumann A J, Birnbaumer L
Department of Cell Biology and Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas 77030.
J Biol Chem. 1992 Apr 15;267(11):7553-62.
We report the molecular cloning of a fragment of human genomic DNA called S12, containing an open reading frame of 1170 nucleotides, which encodes a receptor for serotonin of 390 amino acids. The receptor function of the S12 protein was demonstrated by functional expression in mouse LS12 cells obtained by stable transfection of Ltk- cells, and LM5S12 cells, derived from LM5 cells (Ltk- cells previously transfected with the M5 muscarinic acetylcholine receptor). Adenylyl cyclase studies showed that the S12 receptor is able to mediate inhibition of adenylyl cyclase in response to serotonin in both types of cells. As studied in LM5S12 cells, the S12 receptor did not promote Ca2+ mobilization from internal stores, nor did it significantly modulate the sustained increase in [Ca2+]i elicited by stimulation of the phospholipase C stimulating M5 acetylcholine receptor. The pharmacologic profile of S12 as seen in adenylyl cyclase assays is as follows: (EC50 in nM): serotonin, full agonist (37 nM), 5-carboxamidotryptamine, full agonist (10 nM), sumatriptan, full agonist (50 nM), metergoline, partial agonist (10 nM), methysergide, partial agonist (40 nM), yohimbine, partial agonist (150 nM), metitepin, antagonist (KB = 0.7 to 1.2 nM). We propose that the human S12 serotonin receptor is a receptor of the 5-hydroxytryptamine1D subtype.
我们报道了一段名为S12的人类基因组DNA片段的分子克隆，其包含一个1170个核苷酸的开放阅读框，编码一个由390个氨基酸组成的血清素受体。通过对Ltk-细胞进行稳定转染获得的小鼠LS12细胞以及源自LM5细胞（先前用M5毒蕈碱型乙酰胆碱受体转染的Ltk-细胞）的LM5S12细胞进行功能表达，证明了S12蛋白的受体功能。腺苷酸环化酶研究表明，S12受体能够在这两种细胞中介导血清素引起的腺苷酸环化酶抑制作用。在LM5S12细胞中研究发现，S12受体既不促进细胞内钙库释放Ca2+，也不显著调节由刺激磷脂酶C的M5乙酰胆碱受体引起的细胞内Ca2+持续升高。在腺苷酸环化酶测定中观察到的S12的药理学特征如下：（以纳摩尔为单位的EC50）：血清素，完全激动剂（37 nM），5-羧基色胺，完全激动剂（10 nM），舒马曲坦，完全激动剂（50 nM），麦角苄酯，部分激动剂（10 nM），美西麦角，部分激动剂（40 nM），育亨宾，部分激动剂（150 nM），美替平，拮抗剂（KB = 0.7至1.2 nM）。我们认为人类S12血清素受体是5-羟色胺1D亚型的受体。
