期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 25, 期 6, 页码 715-722出版社
KARGER
DOI: 10.1159/000315091
关键词
Wortmannin; LY294002; Phosphatidylinositol-3-kinase; Phosphoinositide dependent kinase; Peptide transport
资金
- DFG
The phosphoinositol 3 kinase (PI3K) and the phosphoinositide dependent kinase (PDK1) stimulate the serum and glucocorticoid inducible kinase (SGK) and protein kinase B (PKB/Akt) isoforms, kinases stimulating a variety of transporters. Most recently, SGK1 was shown to stimulate the peptide transporters PepT1 and PepT2, and to mediate the glucocorticoid stimulation of PepT1. Basal electrogenic intestinal peptide transport was, however, not dependent on the presence of SGK1. The present study explored whether basal electrogenic intestinal peptide transport is dependent on PI3K or PDK1. To this end, peptide transport in intestinal segments was determined utilizing Ussing chamber analysis. Cytosolic pH (pH(i)) was determined by BCECF fluorescence. The luminal addition of 5 mM dipeptide gly-gly induced a current (Ip) across intestinal segments. Ip was significantly decreased in the presence of PI3 kinase inhibitors Wortmannin (1 mu M) or LY294002 (50 mu M). Exposure of isolated intestinal cells to 5 mM gly-gly was followed by cytosolic acidification (Delta pH(i)), which was significantly blunted by Wortmannin and by LY294002. Both, Ip and Delta pHi were significantly smaller in PDK1 hypomorphic mice ( pdk1(flfl)) than in their wild type littermates (pdk1(wt)). In conclusion, PI3K and PDK1 participate in the regulation of basal peptide transport. Copyright (C) 2010 S. Karger AG, Basel
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