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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 1
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pubmed:dateCreated |
2001-7-2
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pubmed:abstractText |
1. The effects of niflumic acid on the substrate-gated currents mediated by the glutamate transporter EAAT4 expressed in Xenopus laevis oocytes were examined using radiolabelled substrate flux measurements and two-electrode voltage clamp techniques. 2. Niflumic acid significantly enhanced the substrate-gated currents in EAAT4, without affecting the affinity of the substrates towards EAAT4. At a concentration of 300 microM, niflumic acid caused a 19 +/- 5 % reduction in L-[(3)H]glutamate uptake and no significant effect on the uptake of DL-[(3)H]aspartate. Thus, enhancement of the substrate-gated currents in EAAT4 does not correlate with the rate of substrate transport and suggests that the niflumic acid-induced currents are not thermodynamically coupled to the transport of substrate. 3. Niflumic acid and arachidonic acid co-applied with substrate to EAAT4-expressing oocytes had similar functional consequences. However, niflumic acid still enhanced the L-glutamate-gated current to the same extent in the presence and absence of a saturating dose of arachidonic acid, which suggests that the sites of action of the two compounds are distinct. 4. The EAAT4-mediated currents for the two substrates, L-glutamate and L-aspartate, were not enhanced equally by addition of the same dose of niflumic acid and the ionic composition of the niflumic acid-induced currents was not the same for the two substrates. Protons carry the L-glutamate-gated niflumic acid-induced current and both protons and chloride ions carry the L-aspartate-gated niflumic acid-induced current. 5. These results show that niflumic acid can be used to probe the functional aspects of EAAT4 and that niflumic acid and other non-steroid anti-inflammatory drugs could be used as the basis for the development of novel modulators of glutamate transporters.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-10195124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-10480948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-10900021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-1692608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-708689,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-7521911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-7538566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-7546750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-759585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-7791878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-7896776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-8633032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-8824313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-8857541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-8905715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-8910364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9108121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9278537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9463476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9651313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9742136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11432999-9822723
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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/Amino Acid Transport System X-AG,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Transporter 4,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Niflumic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/SLC1A6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-3751
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
534
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
159-67
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11432999-Amino Acid Transport System X-AG,
pubmed-meshheading:11432999-Animals,
pubmed-meshheading:11432999-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11432999-Arachidonic Acid,
pubmed-meshheading:11432999-Aspartic Acid,
pubmed-meshheading:11432999-Drug Synergism,
pubmed-meshheading:11432999-Electric Conductivity,
pubmed-meshheading:11432999-Excitatory Amino Acid Transporter 4,
pubmed-meshheading:11432999-Glutamate Plasma Membrane Transport Proteins,
pubmed-meshheading:11432999-Glutamic Acid,
pubmed-meshheading:11432999-Humans,
pubmed-meshheading:11432999-Ion Channel Gating,
pubmed-meshheading:11432999-Niflumic Acid,
pubmed-meshheading:11432999-Oocytes,
pubmed-meshheading:11432999-Receptors, Glutamate,
pubmed-meshheading:11432999-Substrate Specificity,
pubmed-meshheading:11432999-Symporters,
pubmed-meshheading:11432999-Xenopus laevis
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pubmed:year |
2001
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pubmed:articleTitle |
Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4.
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pubmed:affiliation |
Department of Pharmacology D06, University of Sydney, Sydney, NSW 2006, Australia. mvp1975@hotmail.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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