Multiple effects of N,N' dicyclohexyl carbodiimide on the beta-adrenergic receptor adenylate cyclase system in frog erythrocytes

Treatment of frog erythrocytes with N,N'dicyclohexylcarbodiimide (DCCD) leads to a loss of catecholamine stimulated adenylate cyclase activity without any decrease in fluoride or PGE₁ stimulated cyclase. However, the concentrations of the reagent which inhibit catecholamine sensitive adenylate cyclase activity are 10 fold lower than those which inhibit specific [³H]dihydroalprenolol ([³H]DHA) beta-adrenergic receptor binding. By contrast binding of the radiolabeled beta-adrenergic agonist [³H]hydroxybenzylisoproterenol ([³H]HBI) is considerably more sensitive than antagonist binding to the effects of DCCD. The data suggest that low concentrations of the reagent may modify the effector portion of the beta-adrenergic receptor leading to functional uncoupling of the beta-receptor adenylate cyclase system. At higher concentrations of the reagent the ligand binding site of the beta-receptor appears also to be altered.