Regulation of serotonin-stimulated phosphoinositide hydrolysis: relation to the serotonin 5-HT-2 binding site.
The hypothesis that serotonin (5-HT)-stimulated phosphoinositide hydrolysis is mediated by the 5-HT-2 binding site in cerebral cortex was tested by comparing antagonist Kd values determined by Schild analyses with Ki values at the 5-HT-2 binding site. A significant correlation was found between Kd values and Ki values at competing for 3H-ketanserin binding (R = 0.98), suggesting that the phosphoinositide-linked receptor and the 5-HT-2 site are identical. The 5-HT-2-mediated phosphoinositide response was then used as a measure of 5-HT-2 receptor sensitivity after in vivo treatments that alter the availability of 5-HT. Chronic treatment with the 5-HT-2 antagonist mianserin resulted in a significant decrease (52%) in the density of 5-HT-2 binding sites and a significant decrease (49%) in the maximal phosphoinositide hydrolysis response to 5-HT. Depletion of 5-HT levels with para-chlorophenylalanine or chemical denervation of serotonergic neurons with 5,7-dihydroxytryptamine had no significant effect upon 5-HT-2 receptor density or upon the phosphoinositide response to 5-HT. These data suggest that changes or lack of changes in 5-HT-2 receptor density following in vivo manipulations reflect the functional state of the receptor.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology; D006868:Hydrolysis; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008803:Mianserin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D007650:Ketanserin; D010134:Fenclonine