Greater importance of Ca(2+)-calmodulin in maintenance of ang II- and K(+)-mediated aldosterone secretion: lesser role of protein kinase C.
In this study we have investigated various components of the stimulus-secretion coupling process leading to aldosterone secretion from the calf adrenal glomerulosa cells as evoked by angiotensin II (AII) and potassium (K+). The roles of Ca2+, calmodulin and protein kinase C in the sustained phase rather than initiation of aldosterone secretion were of special interest. Our investigations revealed that the reduction of extracellular Ca2+ by EGTA or interruption of Ca2+ influx by nitrendipine at various time points after stimulation with either AII or K+ markedly compromised aldosterone secretion. Calmodulin inhibitors, calmidazolium and W-7 reduced aldosterone secretion profoundly. Agonists of protein kinase C, phorbol ester or diacylglycerol analogues failed to stimulate aldosterone secretion while the protein kinase C inhibitor, H-7, only partially inhibited aldosterone secretion at a concentration which completely inhibited protein kinase C activity. Calmodulin inhibitors produced significantly greater inhibition of aldosterone secretion than inhibitors of protein kinase C.
Ganguly
A
A
Department of Medicine, University of South Florida College of Medicine, James A. Haley Veterans Hospital, Tampa 33612.
Chiou
S
S
Fineberg
N S
NS
Davis
J S
JS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009568:Nitrendipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D002147:Calmodulin; D004075:Diglycerides; D007093:Imidazoles; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D000804:Angiotensin II; D000450:Aldosterone; C031938:calmidazolium; D004533:Egtazic Acid; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009568:Nitrendipine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium