Pflügers Archiv

, Volume 440, Issue 5, pp 679–684

Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2

Authors

  • Tomohiro Terada
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
  • Kyoko Sawada
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
  • Megumi Irie
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
  • Hideyuki Saito
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
  • Yukiya Hashimoto
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
  • Ken-ichi Inui
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606–8507
Original Article

DOI: 10.1007/s004240000339

Cite this article as:
Terada, T., Sawada, K., Irie, M. et al. Pflügers Arch - Eur J Physiol (2000) 440: 679. doi:10.1007/s004240000339

Abstract

Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir. PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but β-lactam antibiotics without an α-amino group are the only known substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the recognition and affinity of various substrates between rat PEPT1 and rat PEPT2, and to determine the structural requirements influencing the substrate affinity. [14C]Glycylsarcosine uptake by PEPT1- or PEPT2-expressing transfectant was inhibited by di- and tripeptides, but not by amino acids, tetrapeptides or most cyclic dipeptides. All dipeptides and tripeptides examined showed more potent inhibition of [14C]glycylsarcosine uptake via PEPT2 than via PEPT1, irrespective of their charge and structure. Modification of the α-amino group of dipeptides reduced their substrate affinity to both transporters, as compared to unmodified dipeptides, but these dipeptides still showed potent inhibitory effects on PEPT2. Among the nonpeptidic substrates tested, only the eight-amino-octanoic acid displayed stronger inhibition of [14C]glycylsarcosine uptake in PEPT1 than in PEPT2. These findings suggest that α- or β-amino carbonyl function is the key structure responsible for the higher affinity for PEPT2 than for PEPT1.

α- or β-Carbonyl function Cyclic dipeptides Di- and tripeptides Peptide transporters Substrate affinity

Copyright information

© Springer-Verlag 2000