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 (Gi) of adenylate cyclase. Cholera toxin, which activates the stimulatory guanine nucleotide-binding regulatory component (Gs) 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 Gi and Gs modulation of adenylate cyclase.
Joshi
L R
LR
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Katz
M S
MS
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D019810:Sodium Azide; D012965:Sodium Chloride / Q000494:pharmacology*; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001386:Azides; D002414:Cations, Monovalent; D010566:Virulence Factors, Bordetella; D008345:Manganese; D012965:Sodium Chloride; D002772:Cholera Toxin; D019810:Sodium Azide; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide