Abnormal expression of the peptide transporter PepT1 in the colon of massive bowel resection rat: a potential route for colonic mucosa damage by transport of fMLP.

The aim of this study was to investigate the effect of abnormal intestinal oligopeptide transporter (PepT1) on rat colon inflammation by transportion of N-formyl-methionyl-leucyl-phenylalanine (fMLP). We induced upregulation of PepT1 in the colon of rats by 80% small bowel resection and examined colonic PepT1 di-tripeptide transport activity. By Western blot analysis, PepT1 was clearly detected in the colon of bowel resection rats, while it was absent from the colon of bowel transection and reanastomosis rats. The experiment with cephalexin colon perfusion showed that the arterial cephalexin concentration in resection rats was five to nine times that in transection rats. Inhibition of PepT1 by Gly-Gly completely abolished cephalexin absorption from the colon of resection rats. We found that 10 microM fMLP perfusion in the colon of resection rats for 4 hr significantly increased myeloperoxidase (MPO) activity and caused colon wall damage. In contrast, 10 muM fMLP perfusion in the colon of transection rats did not induce any inflammation. A 5 mM Gly-Gly perfusion completely inhibited the MPO activity and colonic wall damage induced by 10 muM fMLP. We conclude that colonic PepT1 induced by bowel resection may provide a mechanism for oligopeptide transport and may serve as a potential cause of colonic mucosa damage by transport of the bacterial product fMLP in rat colon.