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Dual modes of 5-(N-ethyl-N-isopropyl)amiloride modulation of apical dipeptide uptake in the human small intestinal epithelial cell line Caco-2

Lookup NU author(s): Professor 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.

Publication metadata

Author(s): Kennedy DJ, Raldua D, Thwaites DT

Publication type: Article

Publication status: Published

Journal: Cellular and Molecular Life Sciences

Year: 2005

Volume: 62

Issue: 14

Pages: 1621-1631

ISSN (print): 1420-682X

ISSN (electronic): 1420-9071

Publisher: Birkhäuser Basel


DOI: 10.1007/s00018-005-5078-3

PubMed id: 15968466


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