The peptide transporter PEPT1 is expressed in distal colon in rodents and humans and contributes to water absorption

Abstract

The peptide transporter PEPT1, expressed in the brush border membrane of enterocytes, mediates the uptake of di- and tripeptides from luminal protein digestion in the small intestine. PEPT1 was proposed not to be expressed in normal colonic mucosa but may become detectable in inflammatory states such as Crohn's disease or ulcerative colitis. We reassessed colonic expression of PEPT1 by performing a systematic analysis of PEPT1 mRNA and protein levels in healthy colonic tissues in mice, rats, and humans. Immunofluorescence analysis of different mouse strains (C57BL/6N, 129/Sv, BALB/c) demonstrated the presence of PEPT1 in the distal part of the colon but not in proximal colon. Rat and human intestines display a similar distribution of PEPT1 as found in mice. However, localization in human sigmoid colon revealed immunoreactivity present at low levels in apical membranes but substantial staining in distinct intracellular compartments. Functional activity of PEPT1 in colonic tissues from mice was assessed in everted sac preparations using [¹⁴C]Gly-Sar and found to be 5.7-fold higher in distal compared with proximal colon. In intestinal tissues from Pept1-/- mice, no [¹⁴C]Gly-Sar transport was detectable but feces samples revealed significantly higher water content than in wild-type mice, suggesting that PEPT1 contributes to colonic water absorption. In conclusion, our studies unequivocally demonstrate the presence of PEPT1 protein in healthy distal colonic epithelium in mice, rats, and humans and proved that the protein is functional and contributes to electrolyte and water handling in mice.

Species differences in the pharmacokinetics of cefadroxil as determined in wildtype and humanized PepT1 mice

“…However, expression of PepT1 in the large intestine is controversial and may be species- and/or region-dependent [43]. In the current study, cefadroxil permeability was high in the duodenum, jejunum and ileum in both wildtype and huPepT1 mice, agreeing with the protein expression pattern of PepT1 in these two genotypes [5,12].…”

Epithelial Transport in Inflammatory Bowel Diseases

“…In support of this, absorption of radiolabeled PepT1 substrate, Gly-Sar peptide, was higher in the everted sacs from the murine distal colon than in the proximal segment, and higher than in PepT1 −/− mice. Moreover, the study also suggested an involvement of PepT1 in the colonic electrolyte and water transport in mice (48). The mechanism for increased water content in the stools of PepT1 −/− mice, as well as the basis for these controversial findings remains to be elucidated.…”

“…Interestingly, the concept of inducible expression of PepT1 in the colon has been recently challenged in a report by Wuensch et al (48). This group demonstrated detectable apical expression of PEPT1 in the distal (but not proximal) colon in three strains of mice, in rats, and in humans under non-inflammatory conditions.…”

Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance

“…By contrast, di-and tripeptides absorption depends exclusively on the intestinal H ϩ /peptide cotransporter-1 Slc15a1 (PEPT1). This transporter is highly expressed in the small intestine (duodenum, jejunum, and ileum) and also expressed in the distal part of the colon (61). PEPT1 is a high-capacity transporter since it is responsible for the absorption of 70% of dietary nitrogen supplied to the body.…”