Mineralocorticoid-induced increase in beta-adrenergic receptors of cultured rat arterial smooth muscle cells.
We have investigated the effect of mineralocorticoids on beta-adrenergic receptors in cultured arterial smooth muscle cells. Mineralocorticoid (aldosterone) treatment resulted in a significant increase in beta-adrenergic receptors measured by [3H]dihydroalprenolol (DHA) binding. This effect required at least 20 hours of incubation with aldosterone and was completely blocked by cycloheximide (10 micrograms/ml), indicating protein synthesis was required for this response. Aldosterone at the concentration range of 10(-8)-10(-6) M increased [3H]DHA binding, but was ineffective at 10(-9) M. Scatchard analysis of [3H]DHA binding revealed that the observed significant increase in binding was due to an increased number of binding sites (P less than 0.05), and that the affinity was unchanged. The aldosterone (1 x 10(-8) M) effect was completely blocked by the combination of RU 38486 (10(-6) M) and spironolactone (10(-7) M), but not by the glucocorticoid antagonist RU 38486 alone. While basal c-AMP levels were not changed by aldosterone (10(-6) M) treatment, the isoproterenol (10(-6) M) stimulated level of c-AMP was significantly higher in cells treated with aldosterone (P less than 0.05). We conclude that aldosterone, acting through the mineralocorticoid receptor, has a direct effect on arterial smooth muscle cells mediated through modulation of beta-adrenergic receptors of these cells.
Jazayeri
A
A
University of Texas Medical Branch, Department of Human Biological Chemistry & Genetics, Galveston 77550.
Meyer
W J
WJ
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; D004082:Dihydroalprenolol; D003513:Cycloheximide; D000242:Cyclic AMP