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  • Title: H/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na/H exchanger.
    Author: Thwaites DT, Kennedy DJ, Raldua D, Anderson CM, Mendoza ME, Bladen CL, Simmons NL.
    Journal: Gastroenterology; 2002 May; 122(5):1322-33. PubMed ID: 11984519.
    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 [(14)C]glycylsarcosine transport and uptake, (22)Na(+)-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 transapical 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.
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