Correlation between cytosolic free Ca2+ and aldosterone production in bovine adrenal glomerulosa cells. Evidence for a difference in the mode of action of angiotensin II and potassium.
Quantitative changes in cytosolic free calcium [( Ca2+]i), membrane potential, and aldosterone production in response to angiotensin II and extracellular potassium were measured in intact bovine adrenal glomerulosa cells loaded with the fluorescent calcium indicator quin 2. Angiotensin II (10(-9) M) induced a rapid rise in [Ca2+]i from 124 +/- 26 nM to 204 +/- 63 nM (n = 7), which was followed by steroid production, as measured in dynamic studies with superfused adrenal cells, and by slower changes in membrane potential, as assessed with the fluorescent probe 3,3'-dipropylthiadicarbocyanine. Both [Ca2+]i rises and functional response were blocked by the antagonist analogue [Sar1,Ala8]angiotensin II in a dose-dependent manner. Potassium (3-10 mM) provoked dose-dependent increases in [Ca2+]i, with ED50 of 6.5 mM, associated with rapid changes in membrane potential, a response superimposable upon the dose-related aldosterone production induced by potassium in static incubations of quin 2-loaded glomerulosa cells (ED50 = 6.8 mM). Verapamil (2 X 10(-5) M) and nifedipine (10(-7)-10(-6) M) decreased resting [Ca2+]i and blocked entirely the rise in [Ca2+]i induced by potassium, but did not suppress the [Ca2+]i rises induced by angiotensin II. These findings indicate that two important physiological regulators of aldosterone secretion, extracellular potassium, by the opening of voltage-dependent calcium channels, and angiotensin II, by a receptor-mediated mechanism, induce rapid rises in cytosolic free calcium, which precede, and presumably trigger the steroidogenic response.
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000634:Aminoquinolines; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology; D005456:Fluorescent Dyes; D015759:Ionomycin; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D012504:Saralasin / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D004987:Ethers; D005456:Fluorescent Dyes; D000804:Angiotensin II; D000450:Aldosterone; D015759:Ionomycin; D014700:Verapamil; D012504:Saralasin; D009543:Nifedipine; C035739:Quin2; D011188:Potassium; D002118:Calcium