De Léan A, Racz K, McNicoll N, Desrosiers M L
Endocrinology. 1984 Aug;115(2):485-92. doi: 10.1210/endo-115-2-485.
Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5-2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED50 of 1.4 and 1.5 nM, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (-)isoproterenol greater than (-)epinephrine equals (-)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nM, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 microM. (-)Isoproterenol stimulation of aldosterone production was potently inhibited by the beta-adrenergic antagonists (-)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nM, respectively. The alpha-adrenergic antagonists prazosin, yohimbine, and phentolamine only weakly inhibited (-)isoproterenol stimulation with potencies of 5, 13, and 140 microM, respectively. The potent beta 2-adrenergic antagonist ICI 118.551 and the weaker beta 1-adrenergic antagonist atenolol were roughly equipotent with potencies of 0.27 and 0.44 microM, respectively. Addition of the phosphodiesterase inhibitor Ro 20-1724 at 10 microM doubled the maximum stimulation effect of (-)isoproterenol without changing the potency of the catecholamine or the basal level of aldosterone secretion, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation. These results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells. The physiological significance of direct beta-adrenergic stimulation of aldosterone production is currently being assessed.
采用牛肾上腺被膜下细胞原代培养来研究儿茶酚胺对醛固酮分泌的直接影响。用胶原酶和脱氧核糖核酸酶分散细胞，并以高密度（150 - 200万/ml）培养3天，这些细胞对血管紧张素II和促肾上腺皮质激素表现出高敏感性，其半数有效浓度（ED50）分别为1.4 nM和1.5 nM。肾上腺素能激动剂可使醛固酮分泌增加4至6倍，其效力顺序为（-）异丙肾上腺素大于（-）肾上腺素等于（-）去甲肾上腺素大于（+）异丙肾上腺素，相应的ED50分别为5 nM、240 nM、213 nM和3000 nM。未检测到多巴胺对醛固酮分泌基础水平或刺激水平有可重复的抑制作用，但在浓度高于10 μM时有时会观察到微弱的刺激作用。（-）异丙肾上腺素对醛固酮生成的刺激作用可被β - 肾上腺素能拮抗剂（-）阿普洛尔和（+）阿普洛尔有效抑制，其效力分别为1.8 nM和110 nM。α - 肾上腺素能拮抗剂哌唑嗪、育亨宾和酚妥拉明对（-）异丙肾上腺素刺激的抑制作用较弱，效力分别为5 μM、13 μM和140 μM。强效的β2 - 肾上腺素能拮抗剂ICI 118.551和较弱的β1 - 肾上腺素能拮抗剂阿替洛尔效力大致相当，分别为0.27 μM和0.44 μM。添加10 μM的磷酸二酯酶抑制剂Ro 20 - 1724可使（-）异丙肾上腺素的最大刺激作用加倍，而不改变儿茶酚胺的效力或醛固酮分泌的基础水平，这表明环磷酸腺苷（cAMP）可能作为异丙肾上腺素刺激的介质发挥作用。这些结果表明在牛肾小球带细胞中存在刺激醛固酮分泌的β1 - 肾上腺素能受体。目前正在评估醛固酮生成的直接β - 肾上腺素能刺激的生理意义。
