Peptide transporters and their roles in physiological processes and drug disposition

Xenobiotica. 2008 Jul;38(7-8):1022-42. doi: 10.1080/00498250701875254.

Abstract

1. The peptide transporters belong to the peptide transporter (PTR) family and serve as integral membrane proteins for the cellular uptake of di- and tripeptides in the organism. By their ability also to transport peptidomimetics and other substrates with therapeutic activities or precursors of pharmacologically active agents, they are of considerable importance in pharmacology. 2. PEPT1 is the low-affinity, high-capacity transporter and is mainly expressed in the small intestine, whereas PEPT2 is the high-affinity, low-capacity transporter and has a broader distribution in the organism. 3. Targeted mouse models have revealed PEPT2 to be the dominant transporter for the reabsorption of di- and tripeptides and its pharmacological substrates in the organism, and for the removal of these substrates from the cerebrospinal fluid. Moreover, the peptide transporters undergo physiological and pharmacological regulation and, of great interest, are present in disease states where PEPT1 exhibits ectopic expression in colonic inflammation. 4. The paper reviews the structural characteristics of the peptide transporters, the structural requirements for substrates, the distribution of the peptide transporters in the organism, and finally their regulation in the organism in healthy and pathological situations.

Publication types

  • Review

MeSH terms

  • Animals
  • Colitis / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Mice
  • Oligopeptides / metabolism*
  • Organ Specificity
  • Peptide Transporter 1
  • Symporters / metabolism*

Substances

  • Oligopeptides
  • Peptide Transporter 1
  • SLC15A1 protein, human
  • Slc15a1 protein, mouse
  • Symporters
  • hydrogen-coupled oligopeptide transporter PepT2