Serotonin inhibition of adenylate cyclase in human platelet membranes; relation to 5-HT-1A receptor-mediated activity.
Serotonin inhibited both basal and forskolin-stimulated adenylate cyclase activity in human platelet membranes by approx. 30%, with an EC50 of 54 nM. Addition of NaCl to the assay medium reduced the degree of inhibition. 5-carboxamidotryptamine (5-CT) behaved as a full agonist in this system (EC50 of 5.4 nM) and BMY 7378 as a partial agonist (inducing 19% inhibition); the putative 5-HT-1a receptor agonists metergoline, spiroxatrine and MDL 73005 were inactive. The 5-HT-1a receptor antagonists metitepin and NAN-190 behaved as antagonists with Kb or Ki values of 11.2 and 1.17 nM, respectively. Spiperone behaved as a partial antagonist only. Epinephrine and 5-HT produced convergent, non-additive inhibition of both basal and forskolin-stimulated cyclase.
Dept of Psychiatry, Hadassah University Hospital, Jerusalem, Israel.
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Newman
D000067956:Adenylyl Cyclase Inhibitors; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin; D012965:Sodium Chloride; C047087:5-carboxamidotryptamine; C053428:BMY 7378; D004837:Epinephrine