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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-2
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pubmed:abstractText |
We have studied modulation of purinergic receptors (P(2Y) and P(2X) subtypes) on changes in intracellular Ca(2+) [Ca(2+)](i) and expression and production of COX-2 in human microglia. Measurements using Ca(2+)-sensitive spectrofluorometry showed adenosine triphosphate (ATP) to cause rapid transient increases in [Ca(2+)](i). Application of ATP plus the P(2X) antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), or treatment with adenosine diphosphate-beta-S (ADP-beta-S), a selective P(2Y) agonist, led to a considerable prolongation in [Ca(2+)](i) responses compared with ATP. The prolonged time courses were consistent with sustained activation of store-operated channels (SOC) since SKF96365, an inhibitor of SOC, blocked this component of the response. RT-PCR data showed that microglia expressed no COX-2 either constitutively or following treatment of cells with ATP (100 microM for 8 h). However, treatment using ATP plus PPADS or with ADP-beta-S led to marked expression of COX-2. The enhanced COX-2 with ATP plus PPADS treatment was absent in the presence of SKF96365 or using Ca(2+)-free solution. Immunocytochemistry, using a specific anti-COX-2 antibody, also revealed a pattern of purinergic modulation whereby lack of P(2X) activation enhanced the production of COX-2 protein. These results suggest that modulation of subtypes of purinergic receptors regulates COX-2 in human microglia with a link involving SOC-mediated influx of Ca(2+).
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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/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/DAPI,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Aggregation Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Purinergic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Purinergic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/adenosine 5'-O-(2-thiodiphosphate)
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0894-1491
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
95-103
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12838502-Adenosine Diphosphate,
pubmed-meshheading:12838502-Adenosine Triphosphate,
pubmed-meshheading:12838502-Brain,
pubmed-meshheading:12838502-Calcium,
pubmed-meshheading:12838502-Cell Count,
pubmed-meshheading:12838502-Cell Size,
pubmed-meshheading:12838502-Cell Survival,
pubmed-meshheading:12838502-Cells, Cultured,
pubmed-meshheading:12838502-Cyclooxygenase 2,
pubmed-meshheading:12838502-Drug Interactions,
pubmed-meshheading:12838502-Embryo, Mammalian,
pubmed-meshheading:12838502-Fluorescent Dyes,
pubmed-meshheading:12838502-Gene Expression,
pubmed-meshheading:12838502-Humans,
pubmed-meshheading:12838502-Immunohistochemistry,
pubmed-meshheading:12838502-Indoles,
pubmed-meshheading:12838502-Isoenzymes,
pubmed-meshheading:12838502-Membrane Proteins,
pubmed-meshheading:12838502-Microglia,
pubmed-meshheading:12838502-Platelet Aggregation Inhibitors,
pubmed-meshheading:12838502-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:12838502-Purinergic Agonists,
pubmed-meshheading:12838502-Purinergic Antagonists,
pubmed-meshheading:12838502-RNA, Messenger,
pubmed-meshheading:12838502-Receptors, Purinergic,
pubmed-meshheading:12838502-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12838502-Spectrometry, Fluorescence,
pubmed-meshheading:12838502-Thionucleotides
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pubmed:year |
2003
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pubmed:articleTitle |
Differential activation of subtype purinergic receptors modulates Ca(2+) mobilization and COX-2 in human microglia.
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pubmed:affiliation |
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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