Davies E, Kenyon C J, Fraser R
Steroids. 1985 Jun;45(6):551-60. doi: 10.1016/0039-128x(85)90019-4.
Removal of free calcium ions from the incubation medium of isolated bovine adrenocortical cells with EGTA reduced basal cortisol synthesis and blocked the effects of ACTH; additional calcium restored normal steroid synthesis. Calcium channel blockers, verapamil and nitrendipine and the calmodulin antagonist, trifluoperazine inhibited ACTH-stimulated cortisol synthesis in a dose-dependent manner (IC50s of 6.2, 10 and 5.2 microM, respectively). Steroidogenic effects of dibutyryl cyclic AMP were prevented with 50 microM verapamil or trifluoperazine. Calcium ionophore A23187 at 1 microM increased cortisol synthesis 2-3 fold which was less than the normal response to ACTH. Stimulatory effects of ionophore and cyclic AMP or ACTH were not additive. ACTH-stimulation of cortisol synthesis appears to involve cyclic AMP-dependent uptake of extracellular calcium ions, possibly by a mechanism requiring calmodulin. Increases in intracellular calcium ions cannot wholly mimic ACTH actions.
用乙二醇双四乙酸（EGTA）去除分离的牛肾上腺皮质细胞孵育培养基中的游离钙离子，可降低基础皮质醇合成并阻断促肾上腺皮质激素（ACTH）的作用；补充钙可恢复正常的类固醇合成。钙通道阻滞剂维拉帕米和尼群地平以及钙调蛋白拮抗剂三氟拉嗪以剂量依赖的方式抑制ACTH刺激的皮质醇合成（IC50分别为6.2、10和5.2微摩尔）。50微摩尔的维拉帕米或三氟拉嗪可阻止二丁酰环磷腺苷（dibutyryl cyclic AMP）的类固醇生成作用。1微摩尔的钙离子载体A23187可使皮质醇合成增加2至3倍，这低于对ACTH的正常反应。离子载体与环磷腺苷或ACTH的刺激作用并非相加的。ACTH对皮质醇合成的刺激似乎涉及细胞外钙离子的环磷腺苷依赖性摄取，可能是通过一种需要钙调蛋白的机制。细胞内钙离子的增加不能完全模拟ACTH的作用。
