Pflügers Archiv

, Volume 445, Issue 1, pp 139–146

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

  •  D. Kennedy
  •  F. Leibach
  •  V. Ganapathy
  •  D. Thwaites
Original Article

DOI: 10.1007/s00424-002-0910-1

Cite this article as:
Kennedy, D., Leibach, F., Ganapathy, V. et al. Pflugers Arch - Eur J Physiol (2002) 445: 139. doi:10.1007/s00424-002-0910-1
  • 133 Downloads

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.

Na+/H+ exchange NHE3 Dipeptide transport hPepT1 Caco-2 cell Human intestine Epithelial transport pH 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  D. Kennedy
    • 1
  •  F. Leibach
    • 2
  •  V. Ganapathy
    • 2
  •  D. Thwaites
    • 1
  1. 1.Department of Physiological Sciences, Medical School, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, UK
  2. 2.Medical College of Georgia, Biochemistry and Molecular Biology, Augusta, GA 30912-2100, USA

Personalised recommendations