| First Author | Ishizuka N | Year | 2018 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 315 |
| Issue | 5 | Pages | G799-G809 |
| PubMed ID | 30138575 | Mgi Jnum | J:273393 |
| Mgi Id | MGI:6281488 | Doi | 10.1152/ajpgi.00099.2018 |
| Citation | Ishizuka N, et al. (2018) Luminal Na(+) homeostasis has an important role in intestinal peptide absorption in vivo. Am J Physiol Gastrointest Liver Physiol 315(5):G799-G809 |
| abstractText | Intestinal cell line studies indicated luminal Na(+) homeostasis is essential for proton-coupled peptide absorption, because the driving force of PepT1 activity is supported by the apical Na(+)/H(+) exchanger NHE3. However, there is no direct evidence demonstrating the importance of in vivo luminal Na(+) for peptide absorption in animal experiments. To investigate the relationship between luminal Na(+) homeostasis and peptide absorption, we took advantage of claudin 15-deficient (cldn15(-/-)) mice, whereby Na(+) homeostasis is disrupted. We quantitatively assessed the intestinal segment responsible for peptide absorption using radiolabeled nonhydrolyzable dipeptide (glycylsarcosine, Gly-Sar) and nonabsorbable fluid phase marker polyethylene glycol (PEG) 4000 in vivo. In wild-type (WT) mice, the concentration ratio of Gly-Sar to PEG 4000 decreased in the upper jejunum, suggesting the upper jejunum is responsible for peptide absorption. Gly-Sar absorption was decreased in the jejunum of cldn15(-/-) mice. To elucidate the mechanism underlining these impairments, a Gly-Sar-induced short-circuit ( Isc) current was measured. In WT mice, increments of Gly-Sar-induced Isc were inhibited by the luminal application of a NHE3-specific inhibitor S3226 in a dose-dependent fashion. In contrast to in vivo experiments, robust Gly-Sar-induced Isc increments were observed in the jejunal mucosa of cldn15(-/-) mice. Gly-Sar-induced Isc was inhibited by S3226 or a reduction of luminal Na(+) concentration, which mimics low luminal Na(+) concentrations in vivo . Our study demonstrates that luminal Na(+) homeostasis is important for peptide absorption in native epithelia and that there is a cooperative functional relationship between PepT1 and NHE3. NEW & NOTEWORTHY Our study is the first to demonstrate that luminal Na(+) homeostasis is important for proton-coupled peptide absorption in in vivo animal experiments. |
