EFFECTS OF AN EDRF DONOR, SIN-1, ON CALCIUM MOVEMENTS AND PHOSPHOLIPASE-A2 ACTIVITY IN HUMAN PLATELETS

The aim of this study was to understand the inhibitory effects exerted toward platelet aggregation by SIN-1 (3-morpholinosydnonimine), a donor of endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which is able to stimulate soluble guanylate cyclase. Using platelets loaded with the fluorescent calcium indicator fura-2, an inhibitory effect of SIN-1 could be observed against both calcium influx and calcium mobilization elicited by thrombin. However, maximal inhibition of calcium influx (70%) remained higher than maximal inhibition of calcium mobilization (40%). In addition, SIN-1 inhibited mobilization of arachidonic acid promoted by thrombin, which was apparently not directly related to the effects on calcium movements. A general effect of the drug at an early step of signal transduction is suggested, which would involve a rise in guanosine-3',5'-cyclic monophosphate (cyclic GMP). The significance of these effects during in vivo ingestion of SIN-1 is discussed.