Abstract

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.