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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-4
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pubmed:dateCreated |
2008-9-4
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pubmed:abstractText |
Stimulation of the mast cell IgE-receptor (FcepsilonRI) by antigen leads to stimulation of Ca(2+) entry with subsequent mast cell degranulation and release of inflammatory mediators. Ca(2+) further activates Ca(2+)-activated K(+) channels, which in turn provide the electrical driving force for Ca(2+) entry. Since phosphatidylinositol (PI)-3-kinase has previously been shown to be required for mast cell activation and degranulation, we explored, whether mast cell Ca(2+) and Ca(2+)-activated K(+) channels may be sensitive to PI3-kinase activity. Whole-cell patch clamp experiments and Fura-2 fluorescence measurements for determination of cytosolic Ca(2+) concentration were performed in mouse bone marrow-derived mast cells either treated or untreated with the PI3-kinase inhibitors LY-294002 (10 muM) and wortmannin (100 nM). Antigen-stimulated Ca(2+) entry but not Ca(2+) release from the intracellular stores was dramatically reduced upon PI3-kinase inhibition. Ca(2+) entry was further inhibited by TRPV blocker ruthenium red (10 muM). Ca(2+) entry following readdition after Ca(+)-store depletion with thapsigargin was again decreased by LY-294002, pointing to inhibition of store-operated channels (SOCs). Moreover, inhibition of PI3-kinase abrogated IgE-stimulated, but not ionomycin-induced stimulation of Ca(2+)-activated K(+) channels. These observations disclose PI3-kinase-dependent regulation of Ca(2+) entry and Ca(2+)-activated K(+)-channels, which in turn participate in triggering mast cell degranulation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1421-9778
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pubmed:author |
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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 |
169-76
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18769043-Animals,
pubmed-meshheading:18769043-Antigens,
pubmed-meshheading:18769043-Bone Marrow Cells,
pubmed-meshheading:18769043-Calcium Channels,
pubmed-meshheading:18769043-Cell Degranulation,
pubmed-meshheading:18769043-Chromones,
pubmed-meshheading:18769043-Female,
pubmed-meshheading:18769043-Hexosaminidases,
pubmed-meshheading:18769043-Ion Channel Gating,
pubmed-meshheading:18769043-Male,
pubmed-meshheading:18769043-Mast Cells,
pubmed-meshheading:18769043-Mice,
pubmed-meshheading:18769043-Morpholines,
pubmed-meshheading:18769043-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18769043-Potassium Channels, Calcium-Activated,
pubmed-meshheading:18769043-Protein Kinase Inhibitors,
pubmed-meshheading:18769043-Ruthenium Red
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pubmed:year |
2008
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pubmed:articleTitle |
Phosphatidylinositol-3-kinase regulates mast cell ion channel activity.
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pubmed:affiliation |
Department of Physiology, University of Tübingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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