Hausdorff W P, Catt K J
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Endocrinology. 1988 Dec;123(6):2818-26. doi: 10.1210/endo-123-6-2818.
The steroidogenic actions of angiotensin II (AII) and increased extracellular K+ concentrations [( K+]) in rat adrenal glomerulosa cells are selectively enhanced by the voltage-sensitive calcium channel agonist Bay K 8644 (BK 8644). The relationship between these effects of the dihydropyridine agonist and cytosolic calcium concentration [( Ca2+]i) was investigated in rat and bovine glomerulosa cells. In the rat glomerulosa cells, AII and increased [K+] elicited rapid elevations of [Ca2+]i with distinctive temporal characteristics. Whereas the [Ca2+]i response to [K+] declined to basal over 2-3 min, addition of 10 nM AII caused a biphasic increase in [Ca2+]i, with a rapid transient rise followed by a lower plateau phase that remained above basal for several minutes. BK 8644 alone did not affect [Ca2+]i, but at low concentrations (30 nM) increased the magnitude and duration of the [Ca2+]i response elicited by progressive elevation of extracellular [K+] to 12 mM. In AII-stimulated glomerulosa cells, 30 nM BK 8644 enhanced both phases of the cytosolic calcium response, with a more marked effect on the sustained plateau phase. In contrast to its prominent actions in rat glomerulosa cells, BK 8644 had no effect on AII-stimulated rises in [Ca2+]i in bovine glomerulosa cells, and only slightly enhanced their minor [Ca2+]i responses to potassium. These studies provide evidence that AII activates dihydropyridine-sensitive voltage-sensitive calcium channels in rat, but not bovine, adrenal glomerulosa cells. They also suggest that enhancement by BK 8644 of agonist-stimulated [Ca2+]i changes is responsible for its synergistic effects on aldosterone responses to potassium and AII in rat glomerulosa cells and emphasize the importance of the sustained phase of the cytosolic calcium signal in the steroidogenic action of AII.
血管紧张素II（AII）的类固醇生成作用以及细胞外钾离子浓度升高（[K +]）对大鼠肾上腺球状带细胞的作用，可被电压敏感性钙通道激动剂Bay K 8644（BK 8644）选择性增强。在大鼠和牛的球状带细胞中研究了二氢吡啶激动剂的这些作用与胞质钙浓度（[Ca2 +] i）之间的关系。在大鼠球状带细胞中，AII和[K +]升高引起[Ca2 +] i的快速升高，并具有独特的时间特征。 [Ca2 +] i对[K +]的反应在2-3分钟内降至基础水平，而添加10 nM AII则导致[Ca2 +] i呈双相增加，先是快速短暂升高，随后是较低的平台期，该平台期在数分钟内保持高于基础水平。单独使用BK 8644不会影响[Ca2 +] i，但在低浓度（30 nM）下，会增加细胞外[K +]逐渐升高至12 mM所引起的[Ca2 +] i反应的幅度和持续时间。在AII刺激的球状带细胞中，30 nM BK 8644增强了胞质钙反应的两个阶段，对持续的平台期影响更为明显。与在大鼠球状带细胞中的显著作用相反，BK 8644对牛球状带细胞中AII刺激的[Ca2 +] i升高没有影响，仅略微增强了它们对钾的微小[Ca2 +] i反应。这些研究提供了证据，表明AII可激活大鼠而非牛的肾上腺球状带细胞中的二氢吡啶敏感性电压敏感性钙通道。它们还表明，BK 8644对激动剂刺激的[Ca2 +] i变化的增强作用，是其对大鼠球状带细胞中醛固酮对钾和AII反应的协同作用的原因，并强调了胞质钙信号持续阶段在AII类固醇生成作用中的重要性。
