Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2

Br J Pharmacol. 1999 Nov;128(6):1159-64. doi: 10.1038/sj.bjp.0702895.


1 Glibenclamide is a widely used sulphonylurea for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). This agent has been reported to inhibit the activities of various ion channels and transporters. In the present study, we examined the effects of glibenclamide on the function of the H+/peptide cotransporters PEPT1 and PEPT2 by using stable transfectants. 2 Uptake of [14C]-glycylsarcosine, a typical substrate for peptide transporters, by PEPT1- or PEPT2-expressing transfectant was inhibited by glibenclamide as well as other sulphonylureas including tolbutamide. 3 Kinetic analysis revealed that the inhibition by glibenclamide was noncompetitive. Dixon plot analyses showed that the Ki values of this agent were 25 and 7.8 microM for PEPT1 and PEPT2, respectively. 4 Glibenclamide did not inhibit Na+-coupled alanine and alpha-methyl-D-glucoside transport, suggesting that the inhibitory effects of glibenclamide on peptide transporters were not due to nonspecific interactions. 5 There was little uptake of [3H]-glibenclamide by PEPT-expressing transfectants as compared to mock-transfected cells, suggesting that glibenclamide was not a substrate for these peptide transporters. 6 In summary, glibenclamide inhibited the [14C]-glycylsarcosine transport by PEPT1 and PEPT2 in a noncompetitive fashion, although glibenclamide per se was not transported through these transporters. These findings would provide important information for clinical, physiological and biochemical aspects of peptide transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / pharmacokinetics
  • Animals
  • Biological Transport / drug effects
  • Carbon Radioisotopes
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Dipeptides / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Glyburide / pharmacokinetics
  • Glyburide / pharmacology*
  • Hydrogen-Ion Concentration
  • Kinetics
  • LLC-PK1 Cells / cytology
  • LLC-PK1 Cells / drug effects
  • LLC-PK1 Cells / metabolism
  • Methylglucosides / pharmacokinetics
  • Peptide Transporter 1
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sodium / pharmacology
  • Swine
  • Symporters*
  • Tritium


  • Carbon Radioisotopes
  • Carrier Proteins
  • Dipeptides
  • Methylglucosides
  • Peptide Transporter 1
  • Recombinant Fusion Proteins
  • Slc15a1 protein, rat
  • Symporters
  • hydrogen-coupled oligopeptide transporter PepT2
  • Tritium
  • glycylsarcosine
  • methylglucoside
  • Sodium
  • Alanine
  • Glyburide