Prostaglandin-stimulated GTP hydrolysis associated with activation of adenylate cyclase in human platelet membranes.
In membranes purified from human blood platelets, basal guanosine triphosphate (GTP) hydrolysis is reduced by a factor of approximately 6 by exposure to N-ethylmaleimide (10 mM). This decreased background enables the detection of an additional GTP hydrolysis in the presence of prostaglandin E1 (PGE1). The PGE1-stimulated GTPase has several properties correlated with PGE1-stimulated adenylate cyclase in this preparation. The two enzymes have similar dose-response relationships (half-maximal stimulation at 0.1 microM PGE1). Exposure to cholera toxin blocks the PGE1-stimulated GTPase and activates adenylate cyclase. Both enzymes are activated by submicromolar concentrations of GTP, although the Km for the GTPase is about 10 times greater than that for the adenylate cyclase. The data are discussed in relation to the hypothesis that hormone-stimulated adenylate cyclase (i) is activated as a regulatory component binds a molecular of GTP and (ii) is deactivated as this molecule is hydrolyzed.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000201:enzymology; D005033:Ethylmaleimide / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D014422:Turkeys
D011458:Prostaglandins E; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide