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 cycl ase activity in human platelet membranes by approx. 30%, with an EC(50 ) 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 (EC(50) of 5.4 nM) and BMY 7378 as a partial agonist (i nducing 19% inhibition); the putative 5-HT-1a receptor agonists meterg oline, spiroxatrine and MDL 73005 were inactive. The 5-HT-1a receptor antagonists metitepin and NAN-190 behaved as antagonists with K-b or K -i values of 11.2 and 1.17 nM, respectively. Spiperone behaved as a pa rtial antagonist only. Epinephrine and 5-HT produced convergent, non-a dditive inhibition of both basal and forskolin-stimulated cyclase.