Balla T, Hunyady L, Spät A
Biochem Pharmacol. 1982 Apr 1;31(7):1267-71. doi: 10.1016/0006-2952(82)90014-4.
The effects of verapamil and trifluoperazine were examined on isolated rat adrenal glomerulosa cells so as to assess the role of calcium ion influx and calmodulin in the function of this cell population. Verapamil (10(-5) and 10(-4) moles/1) slightly reduced the basal production rate of aldosterone and strongly inhibited the response to angiotensin II, potassium ions, corticotrophin (ACTH) and dibutyryl cyclic AMP (db-cAMP). The concentration of verapamil required to reduce the response to these agonists by 50% varied between 2 and 6 mumoles/1. Trifluoperazine (30 mumoles/1) slightly increased the basal production rate of aldosterone. The response to angiotensin and potassium was variably antagonized by 3 mumoles/1 trifluoperazine and completely inhibited by the drug at 30 mumoles/1. The antagonist at a concentration of 3 mumoles/1 exerted either a facilitatory or inhibitory effect on the response to ACTH and db-cAMP, depending on the concentration of the agonist. Trifluoperazine at a concentration of 30 mumoles/1 reduced the response to both agonists to a level which was 2-3 fold higher than that observed in appropriate control samples. The present results indicate that (1) calcium influx is an essential event in the aldosterone stimulating action of angiotensin II, potassium ions, ACTH and cyclic AMP; (2) stimulation by angiotensin II and potassium ions are completely dependent on calmodulin; (3) stimulation by ACTH and cyclic AMP is mediated by calmodulin-dependent and independent mechanisms.
研究了维拉帕米和三氟拉嗪对离体大鼠肾上腺球状带细胞的作用，以评估钙离子内流和钙调蛋白在该细胞群功能中的作用。维拉帕米（10⁻⁵和10⁻⁴摩尔/升）略微降低了醛固酮的基础产生率，并强烈抑制了对血管紧张素II、钾离子、促肾上腺皮质激素（ACTH）和二丁酰环磷腺苷（db - cAMP）的反应。使对这些激动剂的反应降低50%所需的维拉帕米浓度在2至6微摩尔/升之间。三氟拉嗪（30微摩尔/升）略微增加了醛固酮的基础产生率。3微摩尔/升的三氟拉嗪对血管紧张素和钾的反应有不同程度的拮抗作用，而在30微摩尔/升时该药物则完全抑制反应。3微摩尔/升浓度的拮抗剂对ACTH和db - cAMP的反应根据激动剂的浓度产生促进或抑制作用。30微摩尔/升浓度的三氟拉嗪使对两种激动剂的反应降低到比适当对照样品中观察到的水平高2至3倍。目前的结果表明：（1）钙内流是血管紧张素II、钾离子、ACTH和环磷腺苷刺激醛固酮产生作用中的一个重要事件；（2）血管紧张素II和钾离子的刺激完全依赖于钙调蛋白；（3）ACTH和环磷腺苷的刺激由钙调蛋白依赖性和非依赖性机制介导。
