Expression of the peptide transporter hPepT1 in human colon: a potential route for colonic protein nitrogen and drug absorption.
Substrates of the proton-coupled peptide transporter, hPepT1, include dietary di- and tripeptides plus therapeutically important drugs such as the beta-lactam antibiotics and angiotensin-converting enzyme inhibitors. Expression and function of hPepT1 in the small bowel is well established. We have compared levels of hPepT1 mRNA expression in regions of human gut by RT-PCR methods and examined the expression of hPepT1 in normal human colon using an anti-hPepT1 antipeptide antibody. hPepT1 mRNA was expressed in the large intestine, although at lower levels than in the small intestine. Quantitatively, expression in ileum was 4.6-fold greater than in sigmoid colon. Immunoreactive hPepT1 was detected in human colon at lower levels than in ileum. The pattern of expression differed between the two tissues: whilst expression in the ileum was localised to the apical enterocyte membrane along the length of the crypt-villus axis, expression in the colonocyte was detected at the apical membrane towards the luminal surface but predominantly at the basal membrane towards the base of the crypt. We conclude that distal regions of the bowel express hPepT1, which may provide a mechanism for colonic protein-nitrogen absorption and for absorption of therapeutically important peptidomimetic drugs.
Ford
Dianne
D
School of Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK. dianne.ford@ncl.ac.uk
Howard
Alison
A
Hirst
Barry H
BH
D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D012809:Colon, Sigmoid / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D000074011:Peptide Transporter 1; D010455:Peptides / Q000493:pharmacokinetics*; D011355:Prodrugs; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters
D002352:Carrier Proteins; D000074011:Peptide Transporter 1; D010455:Peptides; D011355:Prodrugs; D011506:Proteins; D012333:RNA, Messenger; C082186:SLC15A1 protein, human; D027981:Symporters; D009584:Nitrogen