Thastrup O, Foder B, Scharff O
Biochem Biophys Res Commun. 1987 Feb 13;142(3):654-60. doi: 10.1016/0006-291x(87)91464-1.
The ability of the platelet agonists thapsigargin (Tg) and thrombin to elevate the cytoplasmic free calcium level ([Ca2+]i) was examined. Both agonists induced a transient increase of [Ca2+]i with a different time-course, however. Thus, the maximal [Ca2+]i was reached 15 sec and 2 min after stimulation with thrombin and Tg, respectively. The thrombin induced rise of [Ca2+]i was reversible, which indicates that active calcium sequestration and/or extrusion is operating. Tg affected [Ca2+]i in a divergent manner, thus, [Ca2+]i was stabilized on a elevated level without initial formation of a pronounced peak. The decline in [Ca2+]i observed after thrombin stimulation was not impaired by the calmodulin binding drug trifluoperazine but it was strongly reduced by vanadate, which suggests the active calcium transport systems to be insensitive to calmodulin. We put forward the hypothesis that the tumor promoting activity of Tg is attributable to its ability to stabilize [Ca2+]i on a new elevated steady state level.
研究了血小板激动剂毒胡萝卜素（Tg）和凝血酶升高细胞质游离钙水平（[Ca2+]i）的能力。然而，两种激动剂均诱导[Ca2+]i出现短暂升高，但时间进程不同。因此，分别在用凝血酶和Tg刺激后15秒和2分钟达到最大[Ca2+]i。凝血酶诱导的[Ca2+]i升高是可逆的，这表明存在活跃的钙螯合和/或钙外流。Tg以不同的方式影响[Ca2+]i，因此，[Ca2+]i稳定在升高的水平，而没有最初形成明显的峰值。凝血酶刺激后观察到的[Ca2+]i下降不受钙调蛋白结合药物三氟拉嗪的影响，但被钒酸盐强烈降低，这表明活跃的钙转运系统对钙调蛋白不敏感。我们提出假说，即Tg的促肿瘤活性归因于其将[Ca2+]i稳定在新的升高稳态水平的能力。
