Evidence that angiotensin-II and potassium collaborate to increase cytosolic calcium and stimulate the secretion of aldosterone.
Angiotensin-II (AII) and potassium (K+) as stimuli of aldosterone secretion enhance each other's stimulatory potential. In the present study we looked for evidence that AII and K+ act through a common mechanism of signal transduction to affect secretion. Bovine adrenal glomerulosa cells were loaded with the calcium (Ca2+) probe aequorin to permit detection over prolonged time periods of the changes in cytosolic Ca2+ that occur in response to AII and K+. Perfusion fractions were collected for simultaneous measurement of aldosterone production rates. AII (10(-7) M) produced an immediate and transient increase in Ca2+, followed by a Ca2+ plateau that remained above baseline for as long as AII was present. An increase in K+ concentration (from 5 to 12 mM) produced a slow and eventually sustained increase in cytosolic Ca2+, which resembled the plateau produced by AII. Nitrendipine (10(-5) M) completely inhibited the secretory response to AII and K+ (during 60-min incubations) and inhibited the typical K+-induced increase in Ca2+. The sustained increase in Ca2+ with AII (the plateau) required extracellular Ca2+ and was proportional to the prevailing extracellular K+ concentration. When glomerulosa cells were incubated with AII, the aldosterone secretory response to K+ was substantially enhanced (P less than 0.001). In summary, stimulation by both AII and K+ resulted in a sustained increase in Ca2+ influx. AII-induced Ca2+ influx was dependent on the ambient K+ concentration. These results indicate that AII and K+ act together to determine the optimal rate of Ca2+ entry, which may then lead to the appropriate secretory rate of aldosterone.
Pratt
J H
JH
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Rothrock
J K
JK
Dominguez
J H
JH
D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D009568:Nitrendipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D000804:Angiotensin II; D000450:Aldosterone; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium