Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.