A UNIQUE SEROTONIN RECEPTOR IN CHOROID-PLEXUS IS LINKED TO PHOSPHATIDYLINOSITOL TURNOVER
A UNIQUE SEROTONIN RECEPTOR IN CHOROID-PLEXUS IS LINKED TO PHOSPHATIDYLINOSITOL TURNOVER
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DOI：
10.1073/pnas.83.11.4086
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发表时间：
1986-06-01
影响因子：
11.1
通讯作者：
HARTIG, PR
中科院分区：
文献类型：
--
作者：
CONN, PJ;SANDERSBUSH, E;HARTIG, PR
最近在脉络丛和几个脑区发现了一个新的5-羟色胺能结合部位--5-HT1C。该位点的生化和生理作用以前从未被描述过。在本报告中，我们发现5-羟色胺(5-羟色胺，5-羟色胺)可刺激大鼠脉络丛中磷脂酰肌醇的更新。5-羟色胺刺激脉络丛磷脂酰肌醇水解的药理作用与大脑皮层5-羟色胺5-HT2受体介导的药理作用进行了比较。5-羟色胺使脉络丛的磷脂酰肌醇周转率增加6倍，大脑皮层的磷脂酰肌醇周转率增加2.5倍。5-羟色胺在脉络丛(EC50=46 NM)中的效力是大脑皮层(EC50=540 NM)的10倍。5-羟色胺拮抗剂酮色林、米安色林和螺环酮对这两种组织的反应有不同程度的抑制作用。在大脑皮层，这三个基因都表现出纳摩尔亲和力，与它们在5-HT2位点上的能力一致。然而，在脉络丛中，等级顺序(Mianserin>；ketanserin>；>；螺环酮)和绝对效力与5-HT1C结合一致。这些数据表明，脉络丛中的5-HT1C位点是一种功能受体，它利用磷脂酰肌醇的代谢作为其生化效应系统。
A novel serotonergic binding site, the 5-HT1C site, has been characterized recently in choroid plexus and several brain regions. The biochemical and physiological roles of this site have not been previously described. In this report we show that serotonin (5-hydroxytryptamine, 5-HT) stimulates phosphatidylinositol turnover in rat choroid plexus. The pharmacology of serotonin-stimulated phosphatidylinositol hydrolysis in choroid plexus was compared to the pharmacology in cerebral cortex, where this response is mediated by the serotonin 5-HT2 receptor. Serotonin increased phosphatidylinositol turnover in choroid plexus by 6-fold and in cerebral cortex by 2.5-fold. Serotonin was > 10-fold more potent in choroid plexus (EC50 = 46 nM) than in cerebral cortex (EC50 = 540 nM). The serotonin antagonists ketanserin, mianserin, and spiperone inhibited the response in the two tissues with different potencies. In cerebral cortex all three exhibited nanomolar affinities consistent with their potencies at the 5-HT2 site. In choroid plexus, however, the rank order (mianserin > ketanserin > > spiperone) and absolute potencies were consistent with binding to the 5-HT1C site. These data suggest that the 5-HT1C site in choroid plexus is a functional receptor that utilizes phosphatidylinositol turnover as its biochemical effector system.