Influence of the cGMP Analog 8-PCPT-cGMP on Agonist-Induced Increasesin Cytosolic Ionized Ca2+ and on Aggregation of Human Platelets

Abstract

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, thrombin, or collagen, respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonist investigated with half-maximal inhibiting effects of approximately 100 nM. 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 anti- platelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.