Gold(III) inhibits activated human osteosarcoma adenylate cyclase by an action at or near the catalytic component.
In human osteosarcoma membranes, gold(III) (Au(III)) inhibits prostaglandin E2- and isoproterenol-mediated stimulation of adenylate cyclase activity without affecting basal enzyme activity. Forskolin activation of adenylate cyclase is also blocked by Au(III) with ID50 of 1-2 microM. The inhibition by Au(III) is preserved in membranes prepared from pertussis toxin-treated cells. The inhibitory effect of Au(III) is additive to inhibition of adenylate cyclase by 2',5'-dideoxyadenosine. These data provide evidence that the action of Au(III) is at or near the catalytic moiety of the cyclase system and that Au(III) does not act via the guanine nucleotide-binding inhibitory component or the adenosine P-site inhibitory pathway.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015232:Dinoprostone; D006046:Gold / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D012516:Osteosarcoma / Q000201:enzymology*; D011458:Prostaglandins E / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D003839:Deoxyadenosines; D011458:Prostaglandins E; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D016048:Dideoxyadenosine; D006046:Gold; C021008:2',5'-dideoxyadenosine; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007545:Isoproterenol