Alpha-thrombin induced the release of internal Ca2+ stores and the influx of Ca2+ in human platelets, as measured by quin-2 fluorescence. This was accompanied by a stimulated formation of inositol phosphates and phosphatidic acid. The Ca2+ responses were inhibited almost totally by pretreatment of cells with prostacyclin (PGI2). Epinephrine was able to restore the influx of Ca2+ from the external medium, but not the alpha-thrombin-induced release of internal Ca2+ stores. This was despite

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... rine restoring phosphatidic acid formation and, at least partially, the generation of inositol trisphosphate (IP3). This suggested that PGI2 was inhibiting the actions of IP3 in inducing release of Ca2+ from the dense tubular system. Since the effects of PGI2 are thought to be mediated by formation of cAMP, we examined whether cAMP could modulate the release of 45Ca2+ induced by IP3 from permeabilized platelets. IP3 induced about a 30% release of cellular 45Ca2+ over a 4 min period. However, neither pretreatment of cells with PGI2 nor the direct application of dibutyryl cAMP had any effect on the IP3-stimulated 45Ca2+ release. GTP, which released about 10% of total cell 45Ca2+, also was not affected by these agents. These results suggest either that permeabilization of platelets dilutes cytoplasmic components which are necessary for cAMP action, or that PGI2 is inhibiting the release of Ca2+ stores induced by thrombin, presumably via IP3, by a mechanism which is separate to the elevation of intracellular cAMP levels.