Stimulatory and inhibitory effects of sodium salts on adenylate cyclase of rat liver. Implications for salt modulation of guanine nucleotide-binding regulatory component function

We have examined the effects of sodium (Na⁺) salts on rat liver adenylate cyclase. Increasing concentrations of Na⁺ salts produced biphasic stimulation and inhibition of adenylate cyclase and potentiated enzyme activation by GTP and its hydrolysis resistant analog 5'-guanylyl imidodiphosphate. Salt effects were temperature dependent, of rapid onset, and specific for the Na⁺ cation though also partly dependent on the accompanying anion. Sodium salt stimulation of adenylate cyclase and enhancement of GTP activation were attenuated by agents (pertussis toxin and N-ethylmaleimide) which inactivate the inhibitory guanine nucleotide-binding regulatory component (G(i)) of adenylate cyclase. Cholera toxin, which activates the stimulatory guanine nucleotide-binding regulatory component (G(s)) of adenylate cyclase and thereby increases enzyme activity, augmented the inhibitory phase of Na⁺ salt action. These results suggest that the stimulatory and inhibitory effects of Na⁺ salts may be due, respectively, to inhibition of G(i) and G(s) modulation of adenylate cyclase.