Capponi A M, Lew P D, Vallotton M B
Division of Endocrinology, University Hospital, Geneva, Switzerland.
Biochem J. 1987 Oct 15;247(2):335-40. doi: 10.1042/bj2470335.
Angiotensin II (AII) and K+ raise the cytosolic free Ca2+ concentration [( Ca2+]i) and stimulate aldosterone production in isolated bovine adrenal glomerulosa cells. The mechanisms leading to an elevation of [Ca2+]i were analysed with the fluorescent Ca2+ probe quin 2. (1) Whereas [Ca2+]i rose transiently and returned to basal values within 5 min in response to AII, the effect of K+ was sustained for at least 15 min. (2) AII released Ca2+ from intracellular stores, whereas the [Ca2+]i response to K+ depended solely on extracellular [Ca2+]. (3) When added after K+ stimulation, AII provoked a dramatic decrease in [Ca2+]i to below the resting value. The role of [Ca2+]i in stimulating steroidogenesis was determined by manipulating the concentration of this cation. (4) In a cell superfusion system, the aldosterone response to AII is biphasic. Suppressing the transient [Ca2+]i elevation triggered by AII resulted in the disappearance of the initial secretory peak, but the final production rate was similar to that of control cells. (5) Normal basal [Ca2+]i levels were, however, necessary to maintain continuous AII-induced steroidogenesis. (6) When added after AII, the antagonist analogue [Sar1,Ala8]AII suppressed steroidogenesis without affecting [Ca2+]i levels. (7) In contrast, continuously elevated [Ca2+]i values were required for the initiation and the maintenance of K+-stimulated aldosterone production. These results demonstrate important differences in the mechanisms through which AII and K+ activate the Ca2+ messenger system. Moreover, functional correlations have shown that K+, but not AII, depends solely on a sustained [Ca2+]i response for its steroidogenic effect. However, the AII-induced effect is also a Ca2+-requiring process: the initial [Ca2+]i transient accelerates the onset of steroidogenesis, which is subsequently extremely sensitive to [Ca2+]i decreases below normal basal levels.
血管紧张素II（AII）和钾离子可提高牛肾上腺球状带分离细胞的胞质游离钙离子浓度[Ca2+]i，并刺激醛固酮生成。使用荧光钙离子探针喹啉2分析了导致[Ca2+]i升高的机制。（1）AII作用下，[Ca2+]i短暂升高并在5分钟内恢复至基础值，而钾离子的作用则持续至少15分钟。（2）AII从细胞内储存库释放钙离子，而[Ca2+]i对钾离子的反应仅取决于细胞外[Ca2+]。（3）在钾离子刺激后添加AII，会使[Ca2+]i急剧下降至静息值以下。通过控制该阳离子的浓度来确定[Ca2+]i在刺激类固醇生成中的作用。（4）在细胞灌流系统中，醛固酮对AII的反应是双相的。抑制AII引发的[Ca2+]i短暂升高会导致初始分泌峰消失，但最终生成速率与对照细胞相似。（5）然而，正常的基础[Ca2+]i水平对于维持AII诱导的持续类固醇生成是必要的。（6）在AII后添加拮抗剂类似物[Sar1，Ala8]AII可抑制类固醇生成，而不影响[Ca2+]i水平。（7）相反，钾离子刺激的醛固酮生成的起始和维持需要持续升高的[Ca2+]i值。这些结果表明AII和钾离子激活钙离子信使系统的机制存在重要差异。此外，功能相关性表明，钾离子而非AII的类固醇生成作用仅依赖于持续的[Ca2+]i反应。然而，AII诱导的效应也是一个需要钙离子的过程：初始的[Ca2+]i瞬变加速了类固醇生成的起始，随后其对[Ca2+]i降至正常基础水平以下极为敏感。
