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Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na⁺/H⁺ exchange activity

Lookup NU author(s): Professor David Kennedy, Professor David Thwaites

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Abstract

Optimal nutrient absorption across the intestinal epithelium is dependent on the co-ordinated activity of a number of membrane transporters. Di/tripeptide transport across the luminal membrane of the intestinal enterocyte is mediated by the H+-coupled di/tripeptide transporter hPepT1. hPepT1 function is dependent on the existence of a pH gradient (maintained, in part, by the action of the Na+/H+ exchanger NHE3) across the apical membrane of the small intestinal epithelium. The physiological problem addressed here was to determine how two transporters (hPepT1 and NHE3), involved in nutrient absorption and pHi homeostasis, function co-operatively to maximise dipeptide absorption when both operate sub-optimally at typical mucosal surface pH values (pH 6.1-6.8). Functional hPepT1 activity in human intestinal epithelial (Caco-2) cell monolayers was determined by measurement of apical uptake and apical-to-basolateral transport of the dipeptide glycylsarcosine. The dependence of hPepT1 on NHE3 activity was measured (either after Na+ removal or addition of the NHE3-selective inhibitor S1611) using both Caco-2 cell monolayers and hPepT1-expressing Xenopus laevis oocytes. Apical glycylsarcosine uptake in Caco-2 cell monolayers was modulated by apical pH, extracellular Na+, incubation time and S1611. Uptake in hPepT1-expressing oocytes was independent of Na+ or S1611. We conclude that functional NHE3 activity is required to allow optimal absorption of dipeptides across the human intestinal epithelium.

Publication metadata

Author(s): Kennedy DJ, Leibach FH, Ganapathy V, Thwaites DT

Publication type: Article

Publication status: Published

Journal: Pfluegers Archiv: European Journal of Physiology

Year: 2002

Volume: 445

Issue: 1

Pages: 139-146

ISSN (print): 0031-6768

ISSN (electronic): 1432-2013

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00424-002-0910-1

DOI: 10.1007/s00424-002-0910-1

PubMed id: 12397398

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