15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and glycyl-arginyl-glycyl-aspartyl-serine

We examined the mechanisms of ATP release by human platelets using Ro-31-7549, a specific inhibitor of protein kinase C. Ro-31-7549 almost completely inhibited TPA-induced platelet aggregation and ATP release at 5-10 microM in washed platelets and in platelet-rich plasma. However, it suppressed thrombin- and U46619-induced ATP release by only 48% and 21%, respectively, and had little effect on aggregation in washed platelet suspensions containing serum or in platelet-rich plasma. The addition of GRGDS to prevent aggregation inhibited this residual thrombin-induced release by 53% and the residual U46619 release by 100% in the presence of Ro-31-7549. In washed platelet suspensions free of serum or plasma, Ro-31-7549 almost completely inhibited the ATP release and partially suppressed the aggregation induced by these agonists. These results suggested that there are protein kinase C-dependent and -independent mechanisms for ATP release by human platelets and that activation of the latter mechanism may depend on aggregation and plasma factors.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Triphosphate; Blood Platelets; Cell Degranulation; Enzyme Activation; Exocytosis; Humans; Indoles; Maleimides; Oligopeptides; Platelet Aggregation Inhibitors; Prostaglandin Endoperoxides, Synthetic; Protein Kinase C; Thrombin; Thromboxane A2