Pharmacological characterization of solubilized 5-HT1 serotonin binding sites from bovine brain.
Pharmacological characterization of solubilized 5-HT1 serotonin binding sites from bovine brain.
复制标题
牛脑溶解的 5-HT1 血清素结合位点的药理学特征。
DOI：
10.1016/0006-8993(85)90362-2
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发表时间：
1985
期刊：
影响因子：
2.9
通讯作者：
Ciaranello,RD
中科院分区：
文献类型：
--
作者：
Allgren,RL;Kyncl,MM;Ciaranello,RD
This report describes the pharmacologic characterization of [3H]serotonin binding activity solubilized from bovine frontal cortical membranes. The ability of a number of serotonin (5-HT) and lysergic acid diethylamide (LSD) analogs to compete with [3H]serotonin andd-[3H]LSD for binding to membrane and solubilized 5-HT1sites has been investigated. The results indicate that the solubilized binding site is probably of the 5-HT1Btype. Fifteen of the 21 compounds tested exhibit nearly identical affinity for membrane or solubilized 5-HT1binding sites. However, some important differences were observed, and these may help elucidate the molecular structure of the binding site. In particular, some N-substituted tryptamine analogs show a markedly lower affinity for solubilized 5-HT1sites compared to their binding to intact membranes. Further, the solubilized site does not distinguish stereoisomers of LSD: bothd- andl-LSD bind to solubilized 5-HT1sites with comparable high affinities, whereasd-LSD has a markedly higher affinity for the membrane 5-HT1site. Methiothepin, which binds to the 5-HT1site primarily through its amine groups, has virtually no affinity for the solubilized receptor, whereas it is quite potent at competing for [3H]serotonin binding to membrane sites. These observations lead to the conclusions that in bovine cortical membranes, the 5-HT1site contains both indole and amine attachment sites. After solubilization, the indole attachment site retains its binding properties, but the amine attachment site has been significantly altered. The differential stability of the indole and amine attachment sites to solubilization suggests that the membrane 5-HT1binding site is either a single protein with discrete amine and indole attachment sites, or a complex of subunits making up these sites. The solubilized preparation does not seem to contain appreciable amounts of 5-HT2binding activity, as it has only low affinity for all 5-HT2ligands tested.
