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 adenylyl cyclase, and glyceryl trinitrate (GTN), which enhances intraplatelet cyclic guanosine monophosphate levels, on human platelet aggregation and intracellular content of cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Forskolin inhibited, in a dose-dependent way, platelet aggregation in response to collagen and adrenaline in platelet-rich plasma. In whole blood samples, forskolin inhibited collagen-stimulated aggregation. In presence of forskolin the intraplatelet cAMP levels were significantly increased. 3. GTN directly decreased the platelet response to collagen in whole blood samples (IC50 = 122 mumol/l) and it increased the intraplatelet levels of both cGMP and cAMP. 4. GTN at 20 and 40 mumol potentiated the inhibitory effects of forskolin on platelet aggregation in both platelet-rich plasma and whole blood. 5. Our results suggest a synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response.
Anfossi
G
G
Department of Clinical and Biological Sciences, University of Turin, Ospedale S. Luigi Gonzaga, Orbassano (To), Italy.
Massucco
P
P
Mularoni
E
E
Cavalot
F
F
Mattiello
L
L
Trovati
M
M
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D005576:Colforsin; D000242:Cyclic AMP; D005996:Nitroglycerin; D006152:Cyclic GMP