Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production.
Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC.
Cozza
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EN
Department of Internal Medicine, University of South Florida Health Sciences Center, Tampa.
Gomez-Sanchez
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CE
D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism
D016232:Endothelins; D000804:Angiotensin II; D000450:Aldosterone; D011493:Protein Kinase C; D002118:Calcium