INFLUENCE OF THE CGMP ANALOG 8-PCPT-CGMP ON AGONIST-INDUCED INCREASESIN 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 aggregati on in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 muM), thrombin (0.025 IU/ml) or collagen (1-3 mug/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 mu M. The data obtaine d suggest that both platelet Ca2+ exchange and aggregation have a simi lar sensitivity to the cGMP analog. In accordance with previously foun d significant differences between the potencies of nitric oxide (NO)-g enerating substances to inhibit increases in cytosolic ionized Ca2+ an d aggregation, it appears that the antiplatelet effects of NO-releasin g agents could only partially be explained by the elevation of cGMP le vels.