The adrenal glomerulosa cell is a major site of action of angiotensin II (AII), which binds to AT1 receptors to stimulate phosphoinositide hydrolysis and Ca2+ mobilization, and the subsequent production of aldosterone. All also influences adrenal growth and proliferation and promotes thymidine incorporation in adrenocortical cells. In primary cultures of bovine glomerulosa cells, All was found to induce the expression of several early growth response genes (c-fos, c-jun, JunB, and Krox 24). This effect of All was dose-dependent and was blocked by [Sar1, lle8] All and the nonpeptide antagonist DuP 753, indicating that it is mediated by the AT, subtype of the All receptor. ACTH, which elevates cAMP in glomerulosa cells, was a relatively weak inducer of c-fos expression but was as potent as All in stimulating the expression of JunB. ACTH did not further enhance the maximal effect of All on c-fos expression. The role of the All-induced cytoplasmic Ca2+ increase in generating the c-fos response was suggested by the ability of the Ca2+ ionophore ionomycin to induce c-fos expression. However, mobilization of intracellular Ca2+ by the Ca2+ ATPase inhibitor thapsigargin, as well as the stimulation of Ca2+ influx by depolarization with potassium, were less potent stimuli of c-fos expression. Omission of Ca2+ from the extracellular medium, which abolishes the plateau phase of the All-induced Ca2+ signal without affecting the early increase due to Ca2+ mobilization, enhanced the early phase of the All-induced c-fos response, indicating that Ca2+ also has an inhibitory effect on the early gene response. Activation of protein kinase C by phorbol 12-myristate, 13-acetate (PMA) also stimulated c-fos expression, but the combination of PMA and ionomycin did not further increase the c-fos response. Inhibition of protein kinase C by staurosporine, or its depletion by prolonged exposure to PMA, prevented the c-fos response to PMA but only partially inhibited the re-sponse to All, suggesting the involvement of other factors in stimulus-transcription coupling from the At1 receptor. Copyright © 1992 by The Endocrine Society.
CITATION STYLE
Clark, A. J. L., Balla, T., Jones, M. R., & Catt, K. J. (1992). Stimulation of early gene expression by angiotensin II in bovine adrenal glomerulosa cells: Roles of calcium and protein kinase C. Molecular Endocrinology, 6(11), 1889–1898. https://doi.org/10.1210/mend.6.11.1336125
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