Churchill P C, Churchill M C
J Pharmacol Exp Ther. 1983 Jan;224(1):68-72.
It has been suggested recently that calmodulin acts as an intracellular "Ca-receptor," and that many Ca-dependent cellular activities are mediated in some manner by Ca-calmodulin. The renin-secretory activity of juxtaglomerular cells appears to be inversely related to intracellular Ca concentration (Ca); if Ca-calmodulin is the mediator in the secretory process, it follows that secretory rate should be inversely related to Ca-calmodulin activity. The purpose of these experiments was to determine the effects of trifluoperazine, an inactivator of Ca-calmodulin, on renin secretion of rat kidney slices. Over the range 10(-6) to 10(-4) M, trifluoperazine produced a concentration-dependent increase in renin release. As assessed by lactate dehydrogenase release, the trifluoperazine-induced increase in renin release cannot be attributed to increased cell membrane permeability to proteins. Thus, trifluoperazine stimulated renin secretion in a concentration-dependent manner. This is consistent with an inverse relation between Ca-calmodulin activity and renin secretion. However, in the presence of trifluoperazine, isoproterenol still stimulated and antidiuretic hormone, angiotensin II, high extracellular K concentration, ouabain and vanadate still inhibited renin secretion. Provided these stimulatory and inhibitory effects are associated with decreased and increased Ca, respectively, these observations are inconsistent with the hypothesis that the effects of Ca, on renin secretion are mediated by changes in Ca-calmodulin activity, since increases in Ca promote rather than attenuate the binding of trifluoperazine to calmodulin. It is concluded that trifluoperazine-stimulated renin secretion is mediated by a decrease in Cai produced by inhibition of Ca influx and/or stimulation of Ca efflux and/or sequestration.
最近有人提出，钙调蛋白作为一种细胞内的“钙受体”，许多依赖钙的细胞活动在某种程度上是由钙 - 钙调蛋白介导的。球旁细胞的肾素分泌活性似乎与细胞内钙浓度（Ca）呈负相关；如果钙 - 钙调蛋白是分泌过程中的介质，那么分泌速率应该与钙 - 钙调蛋白活性呈负相关。这些实验的目的是确定钙调蛋白灭活剂三氟拉嗪对大鼠肾切片肾素分泌的影响。在10^(-6)至10^(-4) M范围内，三氟拉嗪使肾素释放呈浓度依赖性增加。通过乳酸脱氢酶释放评估，三氟拉嗪诱导的肾素释放增加不能归因于细胞膜对蛋白质的通透性增加。因此，三氟拉嗪以浓度依赖性方式刺激肾素分泌。这与钙 - 钙调蛋白活性和肾素分泌之间的负相关一致。然而，在存在三氟拉嗪的情况下，异丙肾上腺素仍能刺激，而抗利尿激素、血管紧张素II、高细胞外钾浓度、哇巴因和钒酸盐仍能抑制肾素分泌。假设这些刺激和抑制作用分别与钙的减少和增加有关，这些观察结果与钙对肾素分泌的影响是由钙 - 钙调蛋白活性变化介导的假设不一致，因为钙的增加促进而不是减弱三氟拉嗪与钙调蛋白的结合。得出的结论是，三氟拉嗪刺激的肾素分泌是由抑制钙内流和/或刺激钙外流和/或钙螯合导致的细胞内钙减少介导的。
