Rat renal peritubular transport and metabolism of plasma [35S]glutathione.
More than 80% of the plasma glutathione is extracted during a single pass through the kidney. The peritubular component of this extraction was characterized by in situ arterial infusion of [35S]glutathione and [3H]inulin. The peak of 35S-labeled material recovered in the renal venous effluent was delayed approximately 10 S compared with the peak of [3H]inulin. As a result, the initial fractions exhibited a decreased 35S/3H ratio, indicating that 35S-labeled material is transported out of the postglomerular peritubular capillaries. Later fractions exhibited a normalized 35S/3H ratio greater than 1, consistent with the subsequent addition of a 35S-labeled metabolite to the venous circulation. An identical profile was observed when perfusion experiments were repeated using gamma-[35S]glutamyl-S-methylcysteine and [3H]inulin. Renal venous plasma samples obtained from a rat perfused with [35S]glutathione were reduced with sodium borohydride, reacted with monobromobimane, and analyzed by high-pressure liquid chromatography. More than 70% of the recovered 35S-labeled material was identified as cysteine and 20% was recovered as unmetabolized glutathione. Pretreatment of rats with a single injection of AT-125 resulted in 96% inactivation of renal gamma-glutamyltranspeptidase. Under these conditions, the percent of glutathione converted to cysteine (35%) was significantly less than the observed level of renal extraction (61%). Two injections of AT-125 caused a complete inhibition of cysteine formation. However, the residual level of renal extraction (41%) was still significantly greater than the filtration fraction (26%). The peritubular transport of glutathione is stimulated by prior depletion of renal glutathione with buthionine-L-sulfoximine and is competitively inhibited by simultaneous infusion of gamma-glutamylcysteine.(ABSTRACT TRUNCATED AT 250 WORDS)
Rankin
B B
BB
Wells
W
W
Curthoys
N P
NP
D000818:Animals; D001692:Biological Transport; D019328:Buthionine Sulfoximine; D004151:Dipeptides / Q000378:metabolism; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008871:Microvilli / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors
D004151:Dipeptides; D007555:Isoxazoles; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C017341:gamma-glutamylcysteine; C006303:acivicin