ALPHA-ADRENERGIC INHIBITION OF NA+ TRANSPORT - INTERACTION OF VASOPRESSIN AND 3',5'-AMP

It has been proposed that α-adrenergic inhibition of Na+ transport across isolated frog skin is mediated by a decrease in adenyl cyclase activity and a resultant decrease in 3′,5′-AMP synthesis. To test this hypothesis the interaction of phenylephrine, predominantly an α-adrenergic substance, with vasopressin and 3′,5′-AMP was studied in the presence of propranalol, a β-blocker. The short-circuit current (Is) technique was used. Phenoxybenzamine, an α-adrenergic blocking agent, prevented the phenylephrine-induced decrease in Is. Dose-response studies indicated the minimum and maximum effective concentrations to be approx. 1 and 100 μM, respectively. A submaximal concentration of phenylephrine (2.5 μM) decreased Is in the presence of a low vasopressin concentration (1 munit/ml), but the effect was prevented by a higher vasopressin concentration (100 munits/ml). The higher vasopressin concentration did not prevent an Is decrease by the maximal effective phenylephrine concentration (0.1 mM). These findings suggest that vasopressin and α-adrenergic stimulation affect the same Na+ transport regulatory system. In the presence of 0.1 mM phenylephrine, vasopressin did not alter Is. However, a concentration of 3′,5′-AMP which was equipotent or less increased Is in the presence of the same phenylephrine concentration. The findings are compatible with the hypothesis that α-adrenergic stimulation decreases adenyl cyclase activity and 3′,5′-AMP synthesis in the frog-skin epidermis which in turn mediates a decrease in Na+ permeability and net Na+ transport. © 1969.