Monovalent ion enhancement of beta-adrenergic-stimulated adenylate cyclase activity in mouse parotid gland.
Sodium activated basal adenylate cyclase at all concentrations of sodium examined (5-100 mM) and independently of GTP. Stimulation of adenhylate cyclase by the beta-adrenergic agonist, isoproterenol, was enhanced at all concentrations (5-100 mM) of sodium ions tested in the presence of GTP. Maximal enzyme activation under all conditions occurred between 25 and 50 mM NaCl. Enhancement of forskolin-activated adenylate cyclase by sodium did not require GTP nor was it affected by guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), a competitive inhibitor of GTP. The selectivity of adenylate cyclase for monovalent cations was Na+ congruent to K+. Lithium chloride produced an inhibition of hormone-activated adenylate cyclase. Sodium ions also enhanced isoproterenol- and forskolin-activated adenylate cyclase of submandibular gland membranes. In contrast to mouse parotid and submandibular glands, activation of mouse liver and brain adenylate cyclase activities by forskolin and isoproterenol was not enhanced by sodium ions. The tissue differences were not related to differences in potency of the agonists. These results suggest (1) that sodium ions may have a selective and positive regulatory role in hormonal activation of adenylate cyclase in mouse exocrine tissue, and (2) that sodium ions enhance hormonal activation of enzyme by interacting at a site on the adenylate cyclase complex which is independent of the hormone receptor (Rs) and the stimulatory guanine nucleotide binding protein (Ns).
Watson
E L
EL
Department of Oral Biology, University of Washington, Seattle 98195.
Jacobson
K L
KL
Singh
J C
JC
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000037:antagonists & inhibitors; D007545:Isoproterenol / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008099:Liver / Q000187:drug effects; D051379:Mice; D010306:Parotid Gland / Q000187:drug effects* / Q000201:enzymology; D012964:Sodium / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
D002712:Chlorides; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D005576:Colforsin; C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D008094:Lithium; D012964:Sodium; D000262:Adenylyl Cyclases; D018021:Lithium Chloride; D007545:Isoproterenol