Physiological and pharmacological implications of peptide transporters, PEPT1 and PEPT2

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 im plications of both transporters. (i) Comparison of the substrate affinity o f PEPT1 and PEPT2 indicated that PEPT2 had higher affinity than PEPT1 for m ost substrates. (ii) The transport characteristics of beta -lactam antibiot ics in the renal brush border membrane vesicles were well correlated with t hose in a PEPT2-expressing transfectant. These results suggested that PEPT2 predominantly contributed to reabsorption of beta -lactam antibiotics in t he kidney at therapeutic concentrations. (iii) In rats with chronic renal f ailure, glycylsarcosine (Gly-Sar) uptake by the renal brush border membrane s vesicles was maintained, whereas Na+-dependent glucose uptake was markedl y reduced. It is therefore speculated that the function of peptide transpor ters is tolerant to chronic renal failure.