Source:http://linkedlifedata.com/resource/pubmed/id/19088454
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5-6
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| pubmed:dateCreated |
2008-12-17
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| pubmed:abstractText |
Pharmacological 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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-phosphoinositide-dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Omeprazole,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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| pubmed:status |
MEDLINE
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| pubmed:issn |
1421-9778
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2008 S. Karger AG, Basel.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
22
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
725-34
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19088454-Animals,
pubmed-meshheading:19088454-Carbachol,
pubmed-meshheading:19088454-Extracellular Space,
pubmed-meshheading:19088454-Forskolin,
pubmed-meshheading:19088454-Gastric Acid,
pubmed-meshheading:19088454-Hydrogen-Ion Concentration,
pubmed-meshheading:19088454-Isoquinolines,
pubmed-meshheading:19088454-Mice,
pubmed-meshheading:19088454-Omeprazole,
pubmed-meshheading:19088454-Parietal Cells, Gastric,
pubmed-meshheading:19088454-Potassium,
pubmed-meshheading:19088454-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19088454-Quaternary Ammonium Compounds,
pubmed-meshheading:19088454-Sulfonamides,
pubmed-meshheading:19088454-Tetradecanoylphorbol Acetate
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| pubmed:year |
2008
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| pubmed:articleTitle |
Role of PDK1 in regulation of gastric acid secretion.
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| pubmed:affiliation |
Department of Physiology, University of Tübingen, Tübingen, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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