Effects of anti-inflammatory and anti-rheumatic drugs on the activities of purified and membrane-bound Na+/K+ adenosine triphosphatase.
We have examined the effects of anti-inflammatory and anti-rheumatic drugs on membrane-bound and purified Na+/K+-ATPase activity in vitro. Only the gold-containing compounds (gold sodium thiomalate and auranofin) were found to inhibit the enzyme activity in a dose-dependent manner. Sodium thiomalate and triethylphosphine, the ligand compounds for gold sodium thiomalate and auranofin, respectively, had no effect on ATPase activity. The antagonistic properties was abolished by preincubation of the gold compounds with dithiothreitol. Lineweaver-Burke analysis of the inhibitions of purified ATPase by the gold compounds was found to follow uncompetitive kinetics. Inhibition of ATPase by gold may cause disruption of transmembrane cation transport and thus result in impairment of several metabolic processes and cellular functions.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014316:Tritium
D000893:Anti-Inflammatory Agents; D014316:Tritium; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D001310:Auranofin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase