Glucocorticoid modulation of beta-adrenergic receptors of cultured rat arterial smooth muscle cells.
Since both glucocorticoids and catecholamines are involved in the regulation of normal blood pressure, we investigated the modulation of beta-adrenergic receptors of cultured rat arterial smooth muscle cells by glucocorticoids. The synthetic glucocorticoids dexamethasone and RU 28362, at 10(-8) M concentration, increased maximum beta-adrenergic binding but had no effect on the dissociation constant (Kd). Each steroid caused an increase in maximum [3H]dihydroalprenolol binding over the concentration range of 10(-8) to 10(-6) M, but not at 10(-9) M. The glucocorticoid effect on beta-adrenergic receptors of arterial smooth muscle cells required a minimum of 20 hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml), indicating that the glucocorticoid effect required protein synthesis. The effect of dexamethasone on [3H]dihydroalprenolol binding was significantly inhibited by the glucocorticoid antagonist RU 38486. Basal and agonist-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels in arterial smooth muscle cells, before and after glucocorticoid treatment, were measured as an indicator of the physiological significance of the observed glucocorticoid-induced increase in beta-adrenergic receptor binding. While causing no change in the basal cAMP level, treatment of arterial smooth muscle cells with 10(-6) M dexamethasone for 24 hours increased the 10(-6) M isoproterenol-stimulated cAMP levels.
Jazayeri
A
A
Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77550.
Meyer
W J
WJ
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D007545:Isoproterenol