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pubmed-article:19088454pubmed:dateCreated2008-12-17lld:pubmed
pubmed-article:19088454pubmed:abstractTextPharmacological inhibition of phosphoinositide 3-kinase (PI3K) has previously been shown to enhance basal gastric acid secretion. Signaling of PI-3-kinase includes activation of the phosphoinositide dependent kinase PDK1. We thus hypothesized that PDK1 may influence gastric acid secretion. In the present study gastric acid secretion in mice expressing ñ20 % of PDK1 (pdk1(hm)) was compared to gastric acid secretion in their wild type littermates (pdk1(wt)). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in pdk1(hm) and in pdk1(wt) mice. Na(+)-independent pH recovery (DeltapH/min) following an ammonium pulse, which reflects K(+)/H(+)-ATPase activity, was however, significantly faster in pdk1(hm) than in pdk1(wt) mice. In both genotypes, DeltapH/min was abolished in the presence of K(+)/H(+)-ATPase inhibitor omeprazole (100 microM). Increase of local K(+)-concentrations to 35 mM (replacing Na(+)/NMDG) significantly increased DeltapH/min in both, pdk1(hm) and pdk1(wt) mice, and abrogated the differences between genotypes. Similarly, treatment with 5 microM forskolin as well as stimulation of protein kinase C with phorbolester phorbol 12 myristate 13 acetate (100 nM) enhanced DeltapH/min to almost identical values in pdk1(hm) and in pdk1(wt)mice. Protein kinase A inhibitor H89 (50 nM) decreased DeltapH/min in pdk1(hm) to values similar to those in pdk1(wt). In conclusion, deficient activity of PDK1 leads to a marked increase of gastric acid secretion. The present observations thus disclose a novel element in the regulation of gastric H(+) secretion.lld:pubmed
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pubmed-article:19088454pubmed:authorpubmed-author:LangFlorianFlld:pubmed
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pubmed-article:19088454pubmed:authorpubmed-author:RotteAnandAlld:pubmed
pubmed-article:19088454pubmed:authorpubmed-author:BhandaruMadhu...lld:pubmed
pubmed-article:19088454pubmed:authorpubmed-author:AckermannTere...lld:pubmed
pubmed-article:19088454pubmed:copyrightInfoCopyright 2008 S. Karger AG, Basel.lld:pubmed
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pubmed-article:19088454pubmed:volume22lld:pubmed
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pubmed-article:19088454pubmed:pagination725-34lld:pubmed
pubmed-article:19088454pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:19088454pubmed:year2008lld:pubmed
pubmed-article:19088454pubmed:articleTitleRole of PDK1 in regulation of gastric acid secretion.lld:pubmed
pubmed-article:19088454pubmed:affiliationDepartment of Physiology, University of Tübingen, Tübingen, Germany.lld:pubmed
pubmed-article:19088454pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19088454pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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