VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF).
Platelet-activating factor (PAF), a potent endogenous phospholipid released by a variety of mammalian cells, induces platelet activation in vivo and in vitro. Little is known, however, about the physiological modulation of its actions. We have examined the ability of two naturally occurring compounds which stimulate cAMP production, vasoactive intestinal peptide (VIP) and prostacyclin (PGI2), to inhibit PAF-induced platelet aggregation and secretion in vitro. Washed, [3H]serotonin-labeled, rabbit platelets were incubated 60 sec in the presence of VIP, PGI2 or 3-isobutyl-1-methylxanthine (IBMX) and subsequently stimulated with PAF. In separate studies, cAMP levels were determined in similar aliquots of platelets incubated for 30 sec with VIP, PGI2 or IBMX. VIP, PGI2 and IBMX inhibited platelet aggregation and secretion in a dose-dependent manner. Fifty percent inhibition was achieved at final concentrations of 1.7 X 10(6) M VIP, 3.6 X 10(6) M PGI2 and 6.5 X 10(5) M IBMX. IBMX potentiated the inhibitory effects of VIP and PGI2 on PAF-induced platelet activation. VIP and PGI2 elevated platelet cAMP levels four-fold and 50-fold, respectively, in the presence of 10(3) M IBMX. These findings demonstrate that VIP inhibits PAF-induced platelet activation, with a potency comparable to that of PGI2.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood*; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000097:blood; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D010972:Platelet Activating Factor; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D011464:Epoprostenol; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine