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Nephrol Dial Transplant (2000) 15: 11-13
© 2000 European Renal Association-European Dialysis and Transplant Association

Proximal Tubular Transport of Organic Compounds

Physiological and pharmacological implications of peptide transporters, PEPT1 and PEPT2

Ken-ichi Inui, Tomohiro Terada, Satohiro Masuda and Hideyuki Saito

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan

Abstract

The H+/peptide co-transporters PEPT1 and PEPT2 mediate the cellular uptake of small peptides and peptide-like drugs from the glomerular filtrates. In the present study, we investigated the physiological and pharmacological implications of both transporters. (i) Comparison of the substrate affinity of PEPT1 and PEPT2 indicated that PEPT2 had higher affinity than PEPT1 for most substrates. (ii) The transport characteristics of ß-lactam antibiotics in the renal brush border membrane vesicles were well correlated with those in a PEPT2-expressing transfectant. These results suggested that PEPT2 predominantly contributed to reabsorption of ß-lactam antibiotics in the kidney at therapeutic concentrations. (iii) In rats with chronic renal failure, glycylsarcosine (Gly-Sar) uptake by the renal brush border membranes vesicles was maintained, whereas Na+-dependent glucose uptake was markedly reduced. It is therefore speculated that the function of peptide transporters is tolerant to chronic renal failure.

Keywords: chronic renal failure; ß-lactam antibiotics; 5/6 nephrectomy; peptide transporters; renal reabsorption


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