Source:http://linkedlifedata.com/resource/pubmed/id/15737330
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2005-3-1
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pubmed:abstractText |
Endothelin-1 (ET-1) is a 21 amino acids peptide that exerts several biological activities through interaction with specific G-protein coupled receptors. Increased ET-1 expression is frequently associated with pathological situations involving alterations in glutamate levels. In the present study, a brief exposure to ET-1 was found to increase aspartate uptake in C6 glioma cells, which endogenously express the neuronal glutamate transporter EAAC1 (pEC50 of 9.89). The stimulatory effect of ET-1 mediated by ETA receptors corresponds to a 62% increase in the Vmax with no modification of the affinity for the substrate. While protein kinase C activity is known to participate in the regulation of EAAC1, the effect of ET-1 on the glutamate uptake was found to be independent of this kinase activation. In contrast, the inactivation of Go/i type G-protein dependent signaling with pertussis toxin was found to impair ET-1-mediated regulation of EAAC1. An examination of the cell surface expression of EAAC1 by protein biotinylation studies or by confocal analysis of immuno-fluorescence staining demonstrated that ET-1 stimulates EAAC1 translocation to the cell surface. Hence, the disruption of the cytoskeleton with cytochalasin D prevented ET-1-stimulated aspartate uptake. Together, the data presented in the current study suggest that ET-1 participates in the acute regulation of glutamate transport in glioma cells. Considering the documented role of glutamate excitotoxicity in the development of brain tumors, endothelinergic system constitutes a putative target for the pharmacological control of glutamate transmission at the vicinity of glioma cells.
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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/Amino Acid Transport System X-AG,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Transporter 3,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin A,
http://linkedlifedata.com/resource/pubmed/chemical/Slc1a1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
1668
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
195-202
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15737330-Amino Acid Transport System X-AG,
pubmed-meshheading:15737330-Animals,
pubmed-meshheading:15737330-Cell Line, Tumor,
pubmed-meshheading:15737330-Endothelin-1,
pubmed-meshheading:15737330-Excitatory Amino Acid Transporter 3,
pubmed-meshheading:15737330-Glioma,
pubmed-meshheading:15737330-Glutamate Plasma Membrane Transport Proteins,
pubmed-meshheading:15737330-Glutamic Acid,
pubmed-meshheading:15737330-Pertussis Toxin,
pubmed-meshheading:15737330-Rats,
pubmed-meshheading:15737330-Receptor, Endothelin A,
pubmed-meshheading:15737330-Symporters
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pubmed:year |
2005
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pubmed:articleTitle |
Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cells.
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pubmed:affiliation |
Laboratoire de Pharmacologie Expérimentale, Université Catholique de Louvain, 54.10, Avenue Hippocrate 54, 1200 Bruxelles, Belgium. mustapha.najimi@farl.ucl.ac.be
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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