GLUCOCORTICOIDS INCREASE GTP-DEPENDENT ADENYLATE-CYCLASE ACTIVITY IN CULTURED FIBROBLASTS

Abstract

Glucocorticoid [dexamethasone, triamcinolone, corticosterone and hydrocortisone] treatment of cultured fibroblasts [Syrian golden hamster cells] increases intracellular cAMP accumulation induced by isoproterenol or cholera toxin. This increase in agonist activity is not a direct action of glucocorticoids on cAMP metabolism since about 2 days are necessary for maximal effect. Basal cAMP 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 .apprx. 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 (.apprx. 5 nM). An alteration in some component in the GTP-dependent regulatory complex is apparently responsible for the increase in agonist response.