U46619 AND PLATELET AGGREGATION VIA INCREASES IN CYTOSOLIC CALCIUM

血栓素模拟物U46619对细胞内钙离子浓度的影响 和血小板聚集。胞浆Ca++ 浓度通过Quin-2荧光和血小板测定 在聚集计中研究的聚集。 向血小板中添加U46619 悬浮液引起胞浆Ca ~（++）和血小板浓度急剧增加 聚合来用前列腺素I2、PGD 2、PGE 1、 PGF 2 α、二丁酰环磷酸腺苷或毛喉素阻止了 胞浆Ca++和U46619诱导的相关血小板聚集。 在用PGE 2处理的血小板中，8-（二乙基氨基）辛基 3，4，5-三甲氧基苯甲酸盐酸盐（TMB-8）或维拉帕米（V），U46619 产生了缓慢得多的细胞质Ca++的增加。虽然胞浆Ca++ 浓度最终达到等于或大于 在对照组中，没有观察到血小板聚集。这些数据表明 U46619通过增加胞质CA++诱导血小板聚集， CA++进入和从细胞内储存位点释放 可能与胞浆Ca ~（++）增加有关。而且 胞浆Ca++的增加速率和增加幅度 浓度似乎是至关重要的血小板聚集诱导的 U46619我们的数据还表明PGs抑制U46619诱导的血小板聚集， 通过阻止胞质Ca++的增加，这些作用 可能是通过增加cAMP介导的。

The effects of U46619, a thromboxane mimic, on cytosolic Ca++ concentration and platelet aggregation were determined in human platelets. Cytosolic Ca++ concentration was determined via Quin-2 fluorescence and platelet aggregation studied in an aggregometer. Addition of U46619 to the platelet suspension produced a sharp increase in cytosolic Ca++ and platelet aggregation. Pretreatment of platelets with prostaglandin I2, PGD2, PGE1, PGF2alpha, dibutyryl2 cyclic AMP or forskolin prevented the increase in cytosolic Ca++ and the associated platelet aggregation induced by U46619. In platelets treated with PGE2, 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), or verapamil (V), U46619 produced a much slower increase in cytosolic Ca++. Although cytosolic Ca++ concentration eventually reached values equal to, or greater than, those of controls, no platelets aggregation was observed. These data suggest that U46619 induces platelet aggregation through an increase in cytosolic CA++, and that both CA++ entry and its release from intracellular storage sites probably contribute to the increase in cytosolic Ca++. Furthermore, the rate of the increase and the magnitude of the rise in cytosolic Ca++ concentration appear to be crucial in platelet aggregation induced by U46619. Our data also suggest that PGs inhibit U46619-induced platelet aggregation by preventing the increase in cytosolic Ca++, and these effects are probably mediated via an increase in cAMP.