EFFECTS OF FORSKOLIN AND ORGANIC NITRATE ON AGGREGATION AND INTRACELLULAR CYCLIC-NUCLEOTIDE CONTENT IN HUMAN PLATELETS

1. The present study investigated the effect of a combination between forskolin, a naturally occurring diterpene which directly activates ad enylyl cyclase, and glyceryl trinitrate (GTN), which enhances intrapla telet cyclic guanosine monophosphate levels, on human platelet aggrega tion and intracellular content of cyclic nucleotides 3',5'-cyclic aden osine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (c GMP). 2. Forskolin inhibited, in a dose-dependent way, platelet aggreg ation in response to collagen and adrenaline in platelet-rich plasma. In whole blood samples, forskolin inhibited collagen-stimulated aggreg ation. In presence of forskolin the intraplatelet cAMP levels were sig nificantly increased. 3. GTN directly decreased the platelet response to collagen in whole blood samples (IC50 = 122 mu mol/l) and it increa sed the intraplatelet levels of both cGMP and cAMP. 4. GTN at 20 and 4 0 mu mol/l potentiated the inhibitory effects of forskolin on platelet aggregation in both platelet-rich plasma and whole blood. 5. Our resu lts suggest a synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of t he platelet response.