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H+/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na+/H+ exchanger

Lookup NU author(s): Professor David Thwaites, Dr David Kennedy, Dr Demetrio Raldua, Dr Catriona Anderson, Dr Ma Mendoza-Gomez, Dr Catherine Bladen, Professor Nicholas Simmons

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Abstract

Background & Aims: For optimal nutrient absorption to occur, the enterocyte must express a range of specialist ion-driven carrier proteins that function cooperatively in a linked and mutually dependent fashion. Thus, absorption via the human intestinal H+-coupled di/tripeptide transporter (hPepT1) is dependent on maintenance of the trans-apical driving force (the H+-electrochemical gradient) established, in part, by brush-border Na+/H+ exchanger (NHE3) activity. This study aimed to examine whether physiologic regulation of NHE3 activity can limit hPepT1 capacity and, therefore, protein absorption after a meal. Methods: hPepT1 and NHE3 activities were determined in intact human intestinal epithelial Caco-2 cell monolayers by measurements of [14C]glycylsarcosine transport and uptake, 22Na+-influx, H+-influx, and H+-efflux. Expression of NHE regulatory factors was determined by reverse-transcriptase polymerase chain reaction. Results: Optimal dipeptide transport was observed in the presence of a trans-apical pH gradient and extracellular Na+. At apical pH 6.5, and only in Na+-containing media, protein kinase A activation (by forskolin or vasoactive intestinal peptide) or selective NHE3 inhibition (by S1611) reduced transepithelial dipeptide transport and cellular accumulation by a reduction in the capacity (without effect on affinity) of dipeptide uptake. Conclusions: Protein kinase A-mediated modulation of intestinal dipeptide absorption is indirect via effects on the apical Na+/H+ exchanger.


Publication metadata

Author(s): Thwaites DT, Kennedy D, Raldua D, Anderson CMH, Mendoza ME, Bladen C, Simmons N

Publication type: Article

Publication status: Published

Journal: Gastroenterology

Year: 2002

Volume: 122

Issue: 5

Pages: 1322-1333

ISSN (print): 0016-5085

ISSN (electronic): 1528-0012

Publisher: WB Saunders Co.

URL: http://dx.doi.org/10.1053/gast.2002.32992

DOI: 10.1053/gast.2002.32992

PubMed id: 11984519


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