Gudermann T, Levy F O, Birnbaumer M, Birnbaumer L, Kaumann A J
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Mol Pharmacol. 1993 Mar;43(3):412-8.
We reported recently the molecular cloning of a genomic fragment, designated S31, that has an open reading frame of 1095 nucleotides, encoding a protein of 365 amino acids. Amino acid similarity analysis suggested that the S31 protein could be a guanine nucleotide-binding protein-coupled receptor pertaining to the serotonin receptor subfamily. Expression of the S31 open reading frame in murine L cells confirmed this, because it led to the appearance of serotonin-mediated inhibition of adenylyl cyclase activity, which was absent in the recipient L cells. We now report some aspects of the pharmacological profile of this receptor. We found that the relative potencies with which 5-hydroxytryptamine, 5-carboxamidotryptamine, methysergide, ergotamine, 8-hydroxydipropylaminotetralin, and trifluoromethylphenylpiperazine promote inhibition of adenylyl cyclase are as follows: 5-hydroxytryptamine >> methysergide >> ergotamine >> trifluoromethylphenylpiperazine > or = 8-hydroxydipropylaminotetralin > 5-carboxyamidotryptamine. This corresponds to the rank order of potencies assigned for these drugs for the 1E subtype of serotonin receptors discovered by Leonhardt and collaborators in human brain [J. Neurochem. 53:465-471 (1989)].
我们最近报道了一个名为S31的基因组片段的分子克隆，它有一个1095个核苷酸的开放阅读框，编码一个由365个氨基酸组成的蛋白质。氨基酸相似性分析表明，S31蛋白可能是一种属于血清素受体亚家族的鸟嘌呤核苷酸结合蛋白偶联受体。S31开放阅读框在鼠L细胞中的表达证实了这一点，因为它导致了血清素介导的腺苷酸环化酶活性抑制的出现，而受体L细胞中不存在这种抑制。我们现在报告该受体药理学特征的一些方面。我们发现，5-羟色胺、5-羧酰胺色胺、麦角新碱、麦角胺、8-羟基二丙基氨基四氢萘和三氟甲基苯基哌嗪促进腺苷酸环化酶抑制的相对效力如下：5-羟色胺>>麦角新碱>>麦角胺>>三氟甲基苯基哌嗪≥8-羟基二丙基氨基四氢萘>5-羧酰胺色胺。这与Leonhardt及其合作者在人脑中发现的血清素受体1E亚型的这些药物效力顺序相对应[《神经化学杂志》53:465 - 471(1989)]。
