Aptel H B, Johnson E I, Vallotton M B, Rossier M F, Capponi A M
Division of Endocrinology and Diabetology, University Hospital, Geneva, Switzerland.
Mol Cell Endocrinol. 1996 May 17;119(1):105-11. doi: 10.1016/0303-7207(96)03805-1.
Although both angiotensin II (Ang II) and potassium ion (K+) induce marked elevations of cytosolic free calcium concentration, [Ca2+]c, in adrenal zona glomerulosa cells-an effect which is thought to trigger aldosterone synthesis-Ang II is also known to reduce the sustained [Ca2+]c rise induced by K+. We have examined whether this effect of Ang II on the calcium messenger system is reflected at the level of the final biological response, aldosterone synthesis. In superfused isolated rat glomerulosa cells, K+ (8 mM) induced a sustained, 60-fold increase in aldosterone production. In contrast, the maximal response to Ang II (10 nM) amounted to only 10 times the basal production. When added subsequent to K+ stimulation, Ang II provoked an immediate and dramatic drop in aldosterone synthesis, to levels obtained with Ang II alone. Under conditions of maximal K+ stimulation, this effect depended upon Ang II concentration, while the well-known synergistic effect was observed with submaximal concentrations of both agonists. The inhibitory effect of Ang II could be reproduced with dioctanoylglycerol, a selective activator of protein kinase C. By contrast, the aldosterone response to adrenocorticotropic hormone (ACTH) was not affected by Ang II. At submaximal concentrations of ACTH, the steroidogenic effect of Ang II was even additive to that of ACTH. Thus, we have shown that, under conditions of maximal stimulation, Ang II exerts a profound inhibition of steroidogenesis in K(+)-stimulated rat adrenal glomerulosa cells. This counter-regulatory mechanism may ensure adequate levels of aldosterone production in vivo.
虽然血管紧张素II（Ang II）和钾离子（K+）均可使肾上腺球状带细胞胞质游离钙浓度（[Ca2+]c）显著升高——这一效应被认为可触发醛固酮合成——但已知Ang II也可降低由K+诱导的[Ca2+]c的持续升高。我们研究了Ang II对钙信使系统的这一效应是否在最终生物学反应即醛固酮合成水平上有所体现。在灌流的离体大鼠球状带细胞中，K+（8 mM）可使醛固酮生成持续增加60倍。相比之下，对Ang II（10 nM）的最大反应仅为基础生成量的10倍。在K+刺激后添加Ang II，可使醛固酮合成立即大幅下降至单独使用Ang II时的水平。在最大K+刺激条件下，这一效应取决于Ang II浓度，而在两种激动剂亚最大浓度时可观察到众所周知的协同效应。Ang II的抑制作用可用二辛酰甘油（一种蛋白激酶C的选择性激活剂）重现。相比之下，Ang II对促肾上腺皮质激素（ACTH）诱导的醛固酮反应无影响。在ACTH亚最大浓度时，Ang II的类固醇生成效应甚至与ACTH的效应相加。因此，我们已表明，在最大刺激条件下，Ang II对K+刺激的大鼠肾上腺球状带细胞的类固醇生成具有显著抑制作用。这种反调节机制可能确保体内醛固酮生成水平充足。
