Peptidases and peptide transport in renal brush-border membrane vesicles from rats with acute renal failure.

We investigated the influence of acute renal failure induced by injection of uranyl nitrate on renal handling of peptides in rats. Urinary excretion of brush-border peptidases increased significantly as a result of uranyl nitrate treatment. H+-coupled Gly-Sar uptake was reduced in renal brush-border vesicles from uranyl nitrate-treated rats compared to control rats. The impairment of dipeptide uptake was evident whether the uptake was measured in the presence or absence of a H+ gradient. Kinetic analysis indicated that the impairment was due mainly to a decrease in the maximal velocity of the transporter. beta-Casomorphin, a pentapeptide, was hydrolyzed to di- and tripeptides by dipeptidylpeptidase IV and the hydrolytic products were taken up actively into control brush-border vesicles via the peptide transporter. But in uranyl nitrate-treated rats, the capacity to hydrolyze and transport beta-casomorphin was greatly reduced. These results show that the ability of the kidneys to process peptides is significantly impaired as a result of uranyl nitrate-induced acute renal failure.