Fray J C, Lush D J, Share D S, Valentine A N
J Physiol. 1983 Oct;343:447-54. doi: 10.1113/jphysiol.1983.sp014903.
Trifluoperazine, an inhibitor of calmodulin and calmodulin-directed secretion, was used to examine a possible role of calmodulin in renin secretion from isolated perfused kidneys and renal cortical cells. In isolated perfused kidneys trifluoperazine stimulated basal renin secretion in a dose-dependent manner, with 10 microM causing no stimulation and 50 microM causing 167% increase. Trifluoperazine potentiated the elevated renin secretion induced by isoprenaline and low Ca in isolated kidneys. In renal cortical cells trifluoperazine increased basal renin secretion and potentiated the secretion induced by Ca omission. Cells homogenized immediately after 1 h exposure to trifluoperazine had a substantial reduction in soluble renin without any effect on the change in granular renin. In the absence of trifluoperazine, soluble renin increased with O Ca and decreased with 1.5 mM-Ca. It is concluded that trifluoperazine stimulates renin secretion by a cellular mechanism possibly at the level of the juxtaglomerular cell. It is suggested that the role of trifluoperazine, and by inference calmodulin, in the secretion of renin may be quite different from its role in secretion of several other substances.
三氟拉嗪是一种钙调蛋白及钙调蛋白介导分泌的抑制剂，被用于研究钙调蛋白在离体灌注肾及肾皮质细胞肾素分泌中可能发挥的作用。在离体灌注肾中，三氟拉嗪以剂量依赖方式刺激基础肾素分泌，10微摩尔/升无刺激作用，50微摩尔/升可使肾素分泌增加167%。三氟拉嗪可增强异丙肾上腺素和低钙诱导的离体肾中升高的肾素分泌。在肾皮质细胞中，三氟拉嗪增加基础肾素分泌，并增强钙缺失诱导的分泌。暴露于三氟拉嗪1小时后立即匀浆的细胞，可溶性肾素大幅减少，而对颗粒性肾素的变化无任何影响。在无三氟拉嗪的情况下，可溶性肾素随无钙环境增加，随1.5毫摩尔/升钙环境减少。结论是，三氟拉嗪可能通过一种细胞机制，可能在球旁细胞水平刺激肾素分泌。有人提出，三氟拉嗪以及由此推断的钙调蛋白在肾素分泌中的作用，可能与其在其他几种物质分泌中的作用有很大不同。
