Renal clearance of glutathione measured in rats pretreated with inhibitors of glutathione metabolism.
Renal clearance measurements were performed in rats pretreated with various inhibitors of glutathione metabolism. Approximately 97% of the renal gamma-glutamyltranspeptidase was inactivated by infusion of AT-125. Within 4.5 h arterial plasma concentration and urinary excretion of glutathione increased from 4 microM and 1.2 nmol/h to 27 microM and 3,900 nmol/h, respectively. The ratio of excreted to filtered glutathione increased from less than 0.01 to 1. When renal glutathione was decreased to 35% of normal by pretreating rats with D,L-buthionine-S,R-sulfoximine, the subsequent inactivation of the transpeptidase caused only a two-fold increase in arterial plasma glutathione, and urinary excretion increased to only 70% of the filtered load. The filtered load of glutathione was reduced by intravenous infusion of purified gamma-glutamyltranspeptidase. At 1 to 3 h after infusion, arterial glutathione decreased to 0.3 microM. Under these conditions, the amount of glutathione excreted by an AT-125-treated rat was 40-fold greater than the filtered load. When similar experiments were carried out in rats that were pretreated with D,L-buthionine-S,R-sulfoximine and AT-125, urinary excretion of glutathione was decreased 10-fold, but it still exceeded the amount filtered. These results firmly establish that apical secretion contributes to the glutathione catabolized in the tubular lumen.
D000818:Animals; D019328:Buthionine Sulfoximine; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000652:urine; D007555:Isoxazoles / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism / Q000494:pharmacology
D007555:Isoxazoles; D010080:Oxazoles; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin