Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA2 production and platelet activation

摘要

Aim: In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1) had neuroprotective effects in a rodent ischemic model. In the present study we aimed to investigate the inhibitory effect of PGA1 on platelet function. Method: The rate of aggregation of human platelets was measured by using turbidimetry. The rate of adhesion of platelets to cultured endothelial cells was determined by using [3H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB2, a stable metabolite of TXA2, were determined by radioimmunoassay. Alternations in platelet morphology were observed using an electron microscope, and the intraplatelet free calcium concentrations were measured with Fluo-3/AM FCM assay. Results: PGA1 significantly inhibited thrombin-collagen-and ADP-induced aggregation and adhesion of platelets. The morphological changes of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release of 5-hydroxytyptamine from dense granules and the synthesis of TXA2. Conclusion: PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA2 synthesis.