Glutathione S-transferases: an 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 X 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 week of age in rats, prior to maturation of transport capacity. Enzyme activity in rabbit kidney was not different at 1 day and 2 weeks but was increased by 4 weeks 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 ammonium chloride acidosis increased enzyme activity 8-fold but decreased transport capacity. Forty-eight hours after unilateral nephrectomy in rats transport capacity was significantly increased with little effect on enzyme activity. L-Methionine-SR-sulfoximine (1.85 mmol/kg) significantly reduced glutathione concentration in renal cortex but had no effect on transport capacity. Organic anion transport was greater in male than in in female mice yet there was no difference in enzyme activity between sexes. 3-Methylcholanthrene (10,20, 30 and 40 mg/kg) administered to 2-week-old rabbits twice daily for 3 days increased transport in a dose-dependent manner. GSH S-transferase activity was also increased. Penicillin (90,000 I.U. twice daily for 2 days) similarly increased transport but had no stimulating effect on enzyme activity. The apparent lack of correlation between transport capacity and GSH S-transferase in several instances suggests that GSH S-transferase concentration is probably not the rate-limiting step in renal organic anion transport.