N-Chloroacetylhydrazone of oxo-GTP irreversibly inhibits the activating function of GTP-binding protein coupled with adenylate cyclase.
Guanine nucleotides are successfully used in the studies of regulatory N-proteins coupled with adenylate cyclase. In the present work N-chloroacetylhydrazones of oxo-GTP and oxo-GDP are described. After 4 hr preincubation of these nucleotides with plasma membranes from bovine brain caudate nucleus, the ability of adenylate cyclase to be activated by guanylyl-5'-methylene-diphosphonate is blocked. The degree of inhibition depends on preincubation time and increases in the presence of Mg2+. Guanylyl-5'-methylenediphosphonate protects adenylate cyclase from the action of N-chloroacetylhydrazone of oxo-GTP. These findings suggest that adenylate cyclase activation is diminished as a result of covalent modification of the Ns. N-chloroacetyl-hydrazone of oxo-GDP also causes a loss of the adenylate cyclase sensitivity to the fluoride ion and cholera toxin.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002417:Cattle; D002421:Caudate Nucleus / Q000201:enzymology; D004164:Diphosphonates / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D006150:Guanine Nucleotides; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D004164:Diphosphonates; D006150:Guanine Nucleotides; D006153:Guanosine Diphosphate; C004805:5'-guanylylmethylenebisphosphonate; D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate; C046513:(N-((chloroacetyl)amino)-3,5-dihydroxy-2-morpholinyl)methyl guanosine diphosphate; C046512:(N-(chloroacetylamino)-3,5-dihydroxy-2-morpholinyl)methyl guanosine triphosphate; D019204:GTP-Binding Proteins; D008274:Magnesium