Aldosterone rapidly represses protein kinase C activity in neonatal rat cardiomyocytes in vitro.
Aldosterone lowers protein kinase C (PKC) activity in myocyte-enriched cultures from neonatal Sprague-Dawley rat hearts, with activity measured by the transfer of phosphate to myristolated alanine-rich C-kinase substrate, in the presence of Ca2+, phosphatidylserine, and diolein. The effect is rapid, with a significant effect after 1 min exposure, half maximal at < or = 1 nM aldosterone, with steroids showing a hierarchy of potency aldosterone = 9alpha fluorocortisol > deoxycorticosterone > corticosterone > spironolactone. Both Ca2+-dependent and -independent PKC activity appear equally inhibited by aldosterone, and PMA-stimulated increases in PKC activity appear similarly aldosterone-sensitive. No displaceable binding of [3H]aldosterone to purified PKC can be shown, evidence against a direct effect of aldosterone on PKC; aldosterone does not alter basal or PMA-stimulated PKC activity in cardiac fibroblasts, evidence for a cell-specific mediator of the myocyte effect. Taken with the previous demonstration of the potentiation of aldosterone-specific MR-mediated effects by PKC activation, the present data argue for the existence of a complex cross-talk mechanism between aldosterone and factors affecting PKC activity in the heart.
Sato
A
A
Baker Medical Research Institute, Melbourne, Australia.
Liu
J P
JP
Funder
J W
JW
D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D014316:Tritium; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D003345:Corticosterone