Gallo-Payet N, Grazzini E, Côté M, Chouinard L, Chorvátová A, Bilodeau L, Payet M D, Guillon G
Service of Endocrinology, Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada.
J Clin Invest. 1996 Jul 15;98(2):460-6. doi: 10.1172/JCI118812.
The present report details the role of Ca2+ in the early events of ACTH action in human adrenal glomerulosa cells. Threshold stimulations of both aldosterone and cAMP production were obtained with a concentration of 10 pM ACTH, an ED50 of 0.1 nM, and maximal aldosterone stimulation (5.5-fold increase over control) at 10 nM ACTH. ACTH also induced a sustained increase of intracellular calcium ([Ca2+]i) with maximal stimulation of 1.6 +/- 0.1-fold over control values. This increase does not involve mobilization of calcium from intracellular pools since no response was observed in Ca2+-free medium or in the presence of nifedipine, suggesting the involvement of Ca2+ influx by L-type Ca2+ channels. This was confirmed by patch clamp studies that demonstrated that ACTH stimulates L-type Ca2+ channels. Moreover, the Ca2+ ion is not required for ACTH binding to its receptor, but is essential for sustained cAMP production and aldosterone secretion after ACTH stimulation. These results indicate that, in human adrenal glomerulosa cells, a positive feedback loop between adenylyl cyclase-protein kinase A-Ca2+ channels ensures a slow but sustained [Ca2+]i increase that is responsible for sustained cAMP production and aldosterone secretion.
本报告详细阐述了Ca2+在人类肾上腺球状带细胞促肾上腺皮质激素（ACTH）作用早期事件中的作用。醛固酮和环磷酸腺苷（cAMP）生成的阈值刺激是在10 pM ACTH浓度下获得的，半数有效剂量（ED50）为0.1 nM，在10 nM ACTH时醛固酮刺激达到最大值（比对照增加5.5倍）。ACTH还诱导细胞内钙（[Ca2+]i）持续增加，最大刺激比对照值增加1.6±0.1倍。这种增加不涉及细胞内钙库的钙动员，因为在无钙培养基或硝苯地平存在下未观察到反应，提示L型钙通道参与了Ca2+内流。膜片钳研究证实了这一点，该研究表明ACTH刺激L型钙通道。此外，Ca2+离子对于ACTH与其受体的结合不是必需的，但对于ACTH刺激后cAMP的持续生成和醛固酮分泌至关重要。这些结果表明，在人类肾上腺球状带细胞中，腺苷酸环化酶-蛋白激酶A-钙通道之间的正反馈回路确保了[Ca2+]i缓慢但持续的增加，这负责cAMP的持续生成和醛固酮分泌。
