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rdf:type |
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lifeskim:mentions |
umls-concept:C0003695,
umls-concept:C0015283,
umls-concept:C0024367,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0030274,
umls-concept:C1514873,
umls-concept:C1522492,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636
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pubmed:issue |
1
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pubmed:dateCreated |
2003-6-6
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pubmed:abstractText |
Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha dose dependently (EC50 = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca2+ current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules from 70-80 to 280-300. cPLA2alpha-stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2alpha. The action of cPLA2alpha was mimicked by a combination of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2alpha was inhibited by the Cl- channel inhibitor DIDS and in cells pretreated with ClC-3 Cl- channel antisense oligonucleotides. We propose that cPLA2alpha has an important role in controlling the rate of exocytosis in beta-cells. This effect of cPLA2alpha reflects an enhanced transgranular Cl- flux, leading to an increase in the number of granules available for release, and requires the combined actions of arachidonic acid and lysophosphatidylcholine.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels,
http://linkedlifedata.com/resource/pubmed/chemical/ClC-3 channel,
http://linkedlifedata.com/resource/pubmed/chemical/Group IV Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0193-1849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E73-81
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12644445-Animals,
pubmed-meshheading:12644445-Arachidonic Acid,
pubmed-meshheading:12644445-Calcium,
pubmed-meshheading:12644445-Calcium Channels,
pubmed-meshheading:12644445-Chloride Channels,
pubmed-meshheading:12644445-Cytoplasmic Granules,
pubmed-meshheading:12644445-Cytosol,
pubmed-meshheading:12644445-Exocytosis,
pubmed-meshheading:12644445-Female,
pubmed-meshheading:12644445-Group IV Phospholipases A2,
pubmed-meshheading:12644445-Islets of Langerhans,
pubmed-meshheading:12644445-Lipoxygenase Inhibitors,
pubmed-meshheading:12644445-Lysophosphatidylcholines,
pubmed-meshheading:12644445-Lysophospholipids,
pubmed-meshheading:12644445-Membrane Potentials,
pubmed-meshheading:12644445-Mice,
pubmed-meshheading:12644445-Oligonucleotides, Antisense,
pubmed-meshheading:12644445-Patch-Clamp Techniques,
pubmed-meshheading:12644445-Phospholipases A,
pubmed-meshheading:12644445-Phospholipases A2,
pubmed-meshheading:12644445-Stimulation, Chemical
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pubmed:year |
2003
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pubmed:articleTitle |
cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells.
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pubmed:affiliation |
Laboratory of Islet Cell Physiology, Novo Nordisk, Bagsvaerd, Denmark.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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