Rosolowsky L J, Campbell W B
University of Texas Southwestern Medical Center, Department of Pharmacology, Dallas 75235-9041.
Endocrinology. 1992 Apr;130(4):2067-75. doi: 10.1210/endo.130.4.1312440.
The adrenal cortex contains a kallikrein-like enzyme that may lead to bradykinin (BK) formation. This study was designed to determine whether BK acts on adrenocortical cells to stimulate steroid secretion. BK, Lys-BK, a specific BK 2 (B2) receptor agonist, and desArg9-BK, a specific BK 1 (B1) receptor agonist, all stimulated aldosterone secretion from cultured bovine adrenal zona glomerulosa cells. BK and Lys-BK were equipotent (EC50 = 2 x 10(-9) M), whereas desArg9-BK was 1000-fold less potent. The maximal effects of BK and BK analogs were comparable to the maximal effects of adrenocorticotropin or angiotensin II. A B2, but not a B1, receptor antagonist inhibited BK-stimulated aldosterone release. Verapamil and N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate, which reduce intracellular calcium concentrations, reduced BK-stimulated aldosterone secretion. Although BK stimulated both prostacyclin and aldosterone production, indomethacin abolished prostacyclin production without affecting aldosterone secretion. In cultured adrenal fasciculata cells, high concentrations of BK stimulated cortisol release, but B1 or B2 receptor agonists were not effective. BK-stimulated cortisol secretion was reduced by N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate but not by indomethacin. In summary, BK stimulates aldosterone release from cultured adrenal glomerulosa cells via high affinity B2 receptors. The effect is calcium-dependent and independent of prostaglandins. BK also increases cortisol release; however, this stimulation requires high concentrations of BK and may be mediated by an unknown receptor or by a receptor-independent mechanism.
肾上腺皮质含有一种类激肽释放酶，可能导致缓激肽（BK）的形成。本研究旨在确定BK是否作用于肾上腺皮质细胞以刺激类固醇分泌。BK、Lys - BK（一种特异性BK2（B2）受体激动剂）和desArg9 - BK（一种特异性BK1（B1）受体激动剂）均刺激培养的牛肾上腺球状带细胞分泌醛固酮。BK和Lys - BK效力相当（EC50 = 2×10^(-9) M），而desArg9 - BK的效力则低1000倍。BK和BK类似物的最大效应与促肾上腺皮质激素或血管紧张素II的最大效应相当。一种B2受体拮抗剂而非B1受体拮抗剂抑制BK刺激的醛固酮释放。维拉帕米和N，N - 二乙氨基辛基 - 3，4，5 - 三甲氧基苯甲酸酯可降低细胞内钙浓度，它们降低了BK刺激的醛固酮分泌。尽管BK刺激前列环素和醛固酮的产生，但吲哚美辛消除了前列环素的产生而不影响醛固酮分泌。在培养的肾上腺束状带细胞中，高浓度的BK刺激皮质醇释放，但B1或B2受体激动剂无效。N，N - 二乙氨基辛基 - 3，4，5 - 三甲氧基苯甲酸酯可降低BK刺激的皮质醇分泌，但吲哚美辛则无此作用。总之，BK通过高亲和力的B2受体刺激培养的肾上腺球状带细胞释放醛固酮。该效应依赖于钙且与前列腺素无关。BK也增加皮质醇释放；然而，这种刺激需要高浓度的BK，可能由未知受体或受体非依赖机制介导。
