Inhibitory effects of sodium and other monovalent cations on human platelet adenylate cyclase.
Both basal and prostaglandin E1 (PGE1)-stimulated human platelet adenylate cyclase activity are inhibited by Na+ and other monovalent cations. Inhibition occurs when the cations are present in concentrations of 20 to 120 mM. Inhibition of basal activity by epinephrine requires the presence of GTP but not Na+. In the presence of epinephrine and GTP, Na+ further reduces basal activity, and the combined effects of all three ligands results in a 70% reduction of basal activity. Sodium, however, does not increase the fractional inhibition of basal activity attributable to epinephrine. Sodium increases the concentrations of epinephrine and of PGE1 required for half-maximal inhibition and stimulation of adenylate cyclase but does not alter the apparent km for Mg2+ or ATP. The rate and extent of adenylate cyclase activation by the GTP analog guanyl-5'-yl imidodiphosphate is reduced by Na+, although the cation does not prevent the acceleration of activation by guanyl-5'-yl imidodiphosphate induced by PGE1. Other monovalent cations also inhibit the platelet cyclase with an order of potency of Na+ greater than Li+ greater than K+ greater than choline+. In addition to demonstrating that Na+ is not required for hormonal inhibition of platelet adenylate cyclase, these studies demonstrate the multiple inhibitory effects which can be induced by Na+ and other monovalent cations. The pattern of these effects suggests that the cations interfere with functional coupling between receptors, guanine nucleotide binding units, and catalytic units of the adenylate cyclase complex.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood*; D000527:Alprostadil; D001792:Blood Platelets / Q000201:enzymology*; D002414:Cations, Monovalent; D004837:Epinephrine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D002414:Cations, Monovalent; D011458:Prostaglandins E; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D012964:Sodium; D000262:Adenylyl Cyclases; D000527:Alprostadil; D008274:Magnesium; D004837:Epinephrine