Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type and Pept1 Knockout Mice
| Autor: | David Smith, Dilara Jappar, Shu Pei Wu, Yongjun Hu |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Colon Immunoblotting Pharmaceutical Science Ileum Peptide Transporter 1 Intestinal absorption Permeability Jejunum Mice Internal medicine Intestine Small medicine Animals Pharmacology Mice Knockout Intestinal permeability biology Dose-Response Relationship Drug Symporters Reverse Transcriptase Polymerase Chain Reaction Peptide transporter 1 Articles Dipeptides Hydrogen-Ion Concentration medicine.disease Small intestine Perfusion medicine.anatomical_structure Endocrinology Intestinal Absorption Symporter Knockout mouse biology.protein Female |
| Popis: | The purpose of this study was to evaluate the role, relevance, and regional dependence of peptide transporter (PEPT) 1 expression and function in mouse intestines using the model dipeptide glycylsarcosine (GlySar). After isolating specific intestinal segments, in situ single-pass perfusions were performed in wild-type and Pept1 knockout mice. The permeability of [(3)H]GlySar was measured as a function of perfusate pH, dipeptide concentration, potential inhibitors, and intestinal segment, along with PEPT1 mRNA and protein. We found the permeability of GlySar to be saturable (K(m) = 5.7 mM), pH-dependent (maximal value at pH 5.5), and specific for PEPT1; other peptide transporters, such as PHT1 and PHT2, were not involved, as judged by the lack of GlySar inhibition by excess concentrations of histidine. GlySar permeabilities were comparable in the duodenum and jejunum of wild-type mice but were much larger than that in ileum (approximately 2-fold). A PEPT1-mediated permeability was not observed for GlySar in the colon of wild-type mice ( |
| Databáze: | OpenAIRE |
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