GLUTATHIONE S-TRANSFERASES - EVALUATION OF THEIR ROLE IN RENAL ORGANIC ANION TRANSPORT

Abstract

Organic anion transport capacity measured as accumulation of p-aminohippurate by renal cortical slices was less in kidneys from newborn rats and rabbits than adults and increased with age. Glutathione (GSH) S-aryltransferase activity in 100,000 .times. g supernatant of renal homogenates, an estimate of GSH S-transferase concentration in the tissue, was also less in newborn of both species. Enzyme activity increased to adult values by 1 wk of age in rats, prior to maturation of transport capacity. Enzyme activity in rabbit kidney was not different at 1 day and 2 wk but was increased by 4 wk coincident with transport maturation. In rats, 25 mg/kg of 3-methylcholanthrene administered once a day for 3 days significantly increased enzyme activity but had no effect on transport capacity. Chronic NH4Cl acidosis increased enzyme activity 8-fold but decreased transport capacity. After unilateral nephrectomy (48 h) in rats transport capacity was significantly increased with little effect on enzyme activity. L-Methionine-SR-sulfoximine (1.85 mmol/kg) significantly reduced GSH concentration in renal cortex but had no effect on transport capacity. Organic anion transport was greater in male than in female mice yet there was no difference in enzyme activity between sexes. Administration of 3-methylcholanthrene (10, 20, 30 and 40 mg/kg) to 2 wk old rabbits twice daily for 3 days increased transport in a dose-dependent manner. GSH S-transferase activity was also increased. Penicillin (90,000 IU twice daily for 2 days) similarly increased transport but had no stimulating effect on enzyme activity. GSH S-transferase concentration was probably not the rate-limiting step in renal organic anion transport.