The reaction to thromboxane thromboxane A_2 in smooth muscle cells

为了研究血栓素A_2在平滑肌细胞中的反应，我们研究了血小板对血栓素A_2的反应。用尼索地平研究细胞外Ca^<2+>进入血小板的调控。在CaCl_2存在的情况下，将尼索地平或载体加入到载富尔2的血小板中，并加入活化剂，血栓素A_2激动剂（U46619）或凝血酶。在其他实验中，将CaCl_2加入到含有EDTA的血小板样品中。u46619诱发的[Ca^<2+>] i升高被尼索地平抑制，而凝血酶诱发的[Ca^<2+>] i升高未被抑制。血小板活化后，在无Ca^<2+>的培养基中加入CaCl_2，尼索地平可抑制U46619引起的[Ca^<2+>] i的升高，但不能抑制凝血酶引起的升高。此外，尼索地平显著抑制U46619诱导的血小板聚集和分泌，但对凝血酶反应无影响。这些数据表明，Ca^<2+>通过血小板膜的进入受两种或两种以上类型的Ca^<2+>通道的调节，包括血栓素a2激活通道和凝血酶激活通道。只有前一种通道被尼索地平阻断。

To study the reaction thromboxane A_2 in smooth muscle cells, we studied the reaction to thromboxane A_2 in platelets. The regulation of extracelluler Ca^<2+> entry into platelets was studied using nisoldipine. Nisoldipine or vehicle was added to fura2-loaded-platelets in the presence of CaCl_2 and an activator, a thromboxane A_2 agonist (U46619) or thrombin, was also added. In the other experiments, CaCl_2 was added after the activator to platelet samples containing EDTA.The U46619-evoked increase of [Ca^<2+>] i was suppressed by nisoldipine, but the thrombin-evoked [Ca^<2+>] i increase was not suppressed. When CaCl_2 was added to Ca^<2+>-free medium after platelet the activation, the increase of [Ca^<2+>] i due to U46619 was suppressed by nisoldipine, but not that due to thrombin. In addition, nisoldipine significantly suppressed platelet aggregation and secretion induced by U46619, but had no effect on the response to thrombin. These data suggest that Ca^<2+> entry through the platelet membrane is regulated by two or more types of Ca^<2+> channeles, including thromboxane A_2-activated and thrombin-activated channels. Only the former type of channel was blocked by nisoldipine.