title: A unique serotonin receptor in choroid plexus is linked to phosphatidylinositol turnover.
abstract: 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 greater than 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 greater than ketanserin much greater than 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.
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism*; D066298:In Vitro Techniques; D007650:Ketanserin; D008803:Mianserin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
chemical_list: D010716:Phosphatidylinositols; D010880:Piperidines; D011985:Receptors, Serotonin; D008803:Mianserin; D013134:Spiperone; D007650:Ketanserin