Glucocorticoids increase GTP-dependent adenylate cyclase activity in cultured fibroblasts.
Glucocorticoid treatment of cultured fibroblasts increases intracellular cyclic AMP accumulation induced by isoproterenol or cholera toxin. This increase in agonist activity is not a direct action of glucocorticoids on cyclic AMP metabolism since about 2 days are necessary for maximal effect. Basal cyclic AMP levels are not changed. In membrane preparations, GTP-dependent adenylate cyclase activity is increased, basal adenylate cyclase activity is unchanged, and NaF-stimulated activity is decreased. The number of beta-adrenergic receptors is unchanged, but the affinity of receptor for the antagonist dihydroalprenolol is increased about 3-fold. This change in affinity is probably not responsible for the increased response to isoproterenol since the augmented response is noted at 0.1 mM isoproterenol, a concentration much larger than the apparent KD (about 5 nM). The results suggest that an alteration in some component in the GTP-dependent regulatory complex is responsible for the increase in agonist response.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D019204:GTP-Binding Proteins; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D004082:Dihydroalprenolol; D003907:Dexamethasone; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D014222:Triamcinolone Acetonide; D003345:Corticosterone; D006854:Hydrocortisone