Prostaglandin A1 inhibits increases in intracellular calcium concentration,TXA_2 production and plat

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:liangjingyu1
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Aim:In our previous studies we found that cyclopentenane prostaglandin A1(PGA1) had neuroprotective effects in a rodent ischemic model.In the presentstudy we aimed to investigate the inhibitory effect of PGA1 on platelet function.Method:The rate of aggregation of human platelets was measured by usingturbidimetry.The rate of adhesion of platelets to cultured endothelial cells wasdetermined by using [~3H]-adenine labeled platelets.5-Hydroxytryptamine releasefrom platelets was measured with O-phthaldialdehyde fluorospectrophotometry.The levels of TXB_2,a stable metabolite of TXA_2,were determined by radioimmuno-assay.Alternations in platelet morphology were observed using an electronmicroscope,and the intraplatelet free calcium concentrations were measured withFluo-3/AM FCM assay.Results:PGA1 significantly inhibited thrombin-,col-lagen-and ADP-induced aggregation and adhesion of platelets.The morphologi-cal changes of platelets induced by thrombin were blocked by PGA1.PGA1inhibited the release of 5-hydroxytyptamine from dense granules and the synthe-sis of TXA_2.Conclusion:PGA1 inhibits the activation of platelets probablythrough blocking increases in intracellular calcium concentration and TXA_2synthesis. 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 a 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 TXB_2, a stable metabolite of TXA_2, were determined by radioimmuno-assay. Biology 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-, col-lagen- and ADP-induced aggregation and adhesion of platelets. The morphologi-cal changes of platelets induced by thrombin were blocked by PGA1.PGA1 inhibited by the re lease of 5-hydroxytyptamine from dense granules and the synthe- sis of TXA_2.Conclusion: PGA1 inhibits the activation of platelets probablythrough blocking increases in intracellular calcium concentration and TXA_2synthesis.
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