Lookup NU author(s): Dr David Kennedy,
Dr Demetrio Raldua,
Professor David Thwaites
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Selective pharmacological Na+/H+ exchange (NHE) inhibitors were used to identify functional NHE isoforms in human small intestinal enterocytes (Caco-2) and to distinguish between direct and indirect effects on transport via the intestinal di/tripeptide transporter hPepT1. The relative potencies of these inhibitors to inhibit 22Na+ influx identifies NHE3 and NHE1 as the apical and basolateral NHE isoforms. The Na+-dependent (NHE3-sensitive) component of apical dipeptide ([ 14C] Gly-Sar) uptake was inhibited by the selective NHE inhibitors with the same order of potency observed for inhibition of apical 22Na+ uptake. However, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) also reduced [14C]Gly-Sar uptake in the absence of Na + and this inhibition was concentration and pH (maximal at pH 5.5) dependent. NHE3 inhibition by S1611 and S3226 modulates dipeptide uptake indirectly by reducing the transapical driving force (H+ electrochemical gradient). EIPA (at 100 μM) has similar effects, but at higher concentrations (>200 μM) also has direct inhibitory effects on hPepT1. © Birkhäuser Verlag, 2005.
Author(s): Kennedy DJ, Raldua D, Thwaites DT
Publication type: Article
Publication status: Published
Journal: Cellular and Molecular Life Sciences
ISSN (print): 1420-682X
ISSN (electronic): 1420-9071
Publisher: Birkhäuser Basel
PubMed id: 15968466
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