Pike, L.J. and Lefkowitz, R.J. (1980) Parallel Activation and Desensitization of Beta-adrenergic Receptor-coupled GTPase and Adenylate Cyclase of Frog and Turkey Erythrocyte Membranes J. Biol Chem. 255: 6860-6867.

The catecholamine-stimulated GTPase activity in frog and turkey erythrocyte membranes has been characterized with respect to its pharmacological specificity, reaction with group-specific reagents, as well as the effect of agonist-induced desensitization. Stimulation of turkey erythrocyte GTPase exhibited a beta₁ receptor subtype specificity whereas activation of the frog erythrocyte enzyme demonstrated beta₂ specificity. In addition, prostaglandin E₁, which is known to stimulate GTPase activity in these membranes. In both cell types, the K_a values and intrinsic activities of several adrenergic agents for the activation of the GTPase were nearly identical with their K_a values and intrinisic activities for the stimulation of adenylate cyclase. When the frog erythrocyte was desensitized by incubation with 10^-4 M isoproterenol, decreases in beta receptor binding as well as isoproterenol-stimulated GTPase and adenylate cyclase activities were observed. By contrast, in the turkey erythrocyte incubation with isoproterenol-stimulated GTPase and adenylate cyclase activities were observed. By contrast, in the turkey erythrocyte incubation with isoproterenol resulted in a loss of isoproterenol-stimulated GTPase and adenylate cyclase activities with no decrease in beta receptor binding.

Studies with group-specific reagents indicated that the adenylate cyclase alone or the GTPase and adenylate cyclase activities together could be inactivated by treatment with N-ethylmaleimide or phenylglyoxal. Nucleotide regulation of beta receptor binding was found to be inactivated by the same treatments which ablated the GTPase activity.

These data suggest that stimulation of the GTPase and adenylate cyclase occur through the same beta-adrenergic receptors and that agonist-induced desensitization leads to a comparable decrease in both activities. In addition, the modification data are consistent with the hypothesis that guanine nucleotide regulation of adenylate cyclase activity and beta receptor binding are mediated through the same protein.