Source:http://linkedlifedata.com/resource/pubmed/id/15090154
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1 Pt 1
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| pubmed:dateCreated |
2004-4-19
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| pubmed:abstractText |
We have developed an assay system suitable for assessment of compound action on the Edg4 subtype of the widely expressed lysophosphatidic acid (LPA)-responsive Edg receptor family. Edg4 was stably overexpressed in the rat hepatoma cell line Rh 7777, and a Ca(2+)-based FLIPR assay developed for measurement of functional responses. In order to investigate the mechanisms linking Edg4 activation to cytosolic Ca(2+) elevation, we have also studied LPA signalling in a human neuroblastoma cell line that endogenously expresses Edg4. LPA responses displayed similar kinetics and potency in the two cell lines. The Ca(2+) signal generated by activation of LPA-sensitive receptors in these cells is mediated primarily by endoplasmic reticulum. However, there is a substantial inhibition of the LPA response by FCCP, indicating that mitochondria also play a key role in the LPA response. Partial inhibition of the response by cyclosporin A could indicate an active Ca(2+) release role for mitochondria in the LPA response. The inositol 1,4,5-triphosphate receptor antagonist 2-aminoethyl diphenyl borate markedly inhibits, but does not abolish, the Ca(2+) response to LPA, suggesting further complexity to the signalling pathways activated by Edg receptors. In comparing Edg signalling in recombinant and native cells, there is a striking overall similarity in receptor expression pattern, agonist potency, and the effect of modulators on the Ca(2+) response. This indicates that the Edg4-overexpressing Rh7777 cell line is a very useful model system for studying receptor pharmacology and signalling mechanisms, and for investigating the Edg4 receptor's downstream effects.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Coloring Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysophosphatidic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine kinase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1540-658X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
1
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
31-40
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15090154-Calcium,
pubmed-meshheading:15090154-Calcium Signaling,
pubmed-meshheading:15090154-Carcinoma, Hepatocellular,
pubmed-meshheading:15090154-Cell Line, Tumor,
pubmed-meshheading:15090154-Coloring Agents,
pubmed-meshheading:15090154-Endoplasmic Reticulum,
pubmed-meshheading:15090154-Enzyme Inhibitors,
pubmed-meshheading:15090154-Humans,
pubmed-meshheading:15090154-Immunohistochemistry,
pubmed-meshheading:15090154-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:15090154-Liver Neoplasms,
pubmed-meshheading:15090154-Lysophospholipids,
pubmed-meshheading:15090154-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:15090154-Receptors, G-Protein-Coupled,
pubmed-meshheading:15090154-Receptors, Lysophosphatidic Acid,
pubmed-meshheading:15090154-Recombinant Proteins,
pubmed-meshheading:15090154-Signal Transduction,
pubmed-meshheading:15090154-Thapsigargin
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| pubmed:year |
2002
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| pubmed:articleTitle |
Native and recombinant human Edg4 receptor-mediated Ca(2+) signalling.
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| pubmed:affiliation |
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK. peter_simpson@merck.com
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| pubmed:publicationType |
Journal Article
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