4-Aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1

Authors


  • Authors' present addresses D. Meredith: Department of Biochemistry, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.

    C. S. Temple: Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, UK.

Corresponding author C. A. R. Boyd: Department of Human Anatomy, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Email: richard.boyd@anat.ox.ac.uk

Abstract

  • 14-Aminomethylbenzoic acid, a molecule which mimics the spatial configuration of a dipeptide, competitively inhibits peptide influx in both Xenopus laevis oocytes expressing rabbit PepT1 and through PepT1 in rat renal brush border membrane vesicles.
  • 2This molecule is not translocated through PepT1 as measured both by direct HPLC analysis in PepT1-expressing oocytes and indirectly by its failure to trans-stimulate labelled peptide efflux through PepT1 in oocytes and in renal membrane vesicles.
  • 3However 4-aminomethylbenzoic acid does reverse trans-stimulation through expressed PepT1 of labelled peptide efflux induced by unlabelled peptide. Quantitatively this reversal is compatible with 4-aminomethylbenzoic acid competitively binding to the external surface of PepT1.
  • 44-Aminomethylbenzoic acid (the first molecule discovered to be a non-translocated competitive inhibitor of proton-coupled oligopeptide transport) and its derivatives may thus be particularly useful as experimental tools.

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