U46619 AND PLATELET AGGREGATION VIA INCREASES IN CYTOSOLIC CALCIUM

U46619 通过增加胞质钙而导致血小板聚集

• 批准号: 3899214
• 负责人: J YUN
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3899214
• 关键词: blood /lymphatic pharmacology; calcium transporting ATPase; cyclic AMP; cytoplasm; fluorescent dye /probe; forskolin; human tissue; hypertension; platelet aggregation; prostaglandins; thromboxanes; verapamil

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.

血栓素类似物U46619对细胞内钙离子浓度的影响 测定人血小板聚集率。胞内钙离子 浓度通过Quin-2荧光法和血小板测定 在聚合计中研究的聚合体。U46619加入到血小板中 悬浮液使细胞内钙离子和血小板急剧增加 聚合。前列腺素I_2、前列腺素D_2、前列腺素E_1、 PGF2pha、二丁基-2-环-AMP或Forsklin可阻止 U46619诱导的细胞内钙离子和相关的血小板聚集。 前列腺素E_2，8-(二乙氨基)辛基处理的血小板 3，4，5-三甲氧基苯甲酸酯盐酸盐(TMB-8)或维拉帕米(V)，U46619 细胞内钙离子的增加要慢得多。虽然胞内钙离子 浓度最终达到等于或大于 对照组未观察到血小板聚集现象。这些数据表明 U46619通过增加胞内Ca~(++)诱导血小板聚集 无论是CA++的进入还是从细胞内存储位置的释放 可能与细胞内钙离子浓度的升高有关。此外， 胞浆内钙离子升高的速度和幅度 浓度似乎是诱导血小板聚集的关键因素 U46619。我们的数据还表明PGs抑制U46619诱导的血小板 通过阻止胞浆内钙离子的增加而聚集，以及这些效应 可能是通过cAMP的增加来调节的。