title: Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis.
abstract: Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on "inhibitory" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors.
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D007700:Kinetics; D008053:Lipid Mobilization / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D014970:Xanthines; C008514:methylxanthine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D000241:Adenosine