THE INHIBITION BY ACETAZOLEAMIDE OF RENAL PHOSPHATE-ACTIVATED GLUTAMINASE IN RATS

Abstract

Intraperitoneal injection of acetazoleamide (10 mg/100 g body weight) in rats elicits a decreased activity of renal phosphate-activated glutaminase within 1 to 3 hours, followed by a return to normal activity at 8 hours, an increased activity at 16 hours, and a return to normal activity at 24 hours. Urinary excretion of ammonia in acetazoleamide-treated rats is decreased in the 8-hour period following injection (period of decreased enzyme activity) and increased in the subsequent 16-hour period (period of increased glutaminase activity). The net effect is increased urinary excretion of ammonia during the 24-hour period. Acetazoleamide inhibits renal phosphate-activated glutaminase in vitro, 100% inhibition being attained with an inhibitor: substrate ratio 3:1. Inhibition by acetazoleamide in vitro is eliminated with increasing L-glutamine concentration, 100% restoration of activity occurring with an inhibitor: substrate ratio of 1:3. Acetazoleamide had no significant effect upon hepatic phosphate-activated glutaminase and arginase activities in vivo nor upon urinary excretion of urea.