Source:http://linkedlifedata.com/resource/pubmed/id/19523966
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2009-7-27
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pubmed:abstractText |
To better understand the effects of the tryptophan metabolite kynurenic acid (kynA) in the brain, we characterised its actions at five ligand-gated ion channels: NMDA, AMPA, GABA(A), glycine and alpha7 nicotinic acetylcholine receptors. Using whole-cell patch-clamp recordings, we found that kynA was a more potent antagonist at human NR1a/NR2A compared with NR1a/NR2B receptors (IC(50): 158 muM and 681 muM, respectively; in 30 muM glycine). KynA inhibited AMPA-evoked currents to a similar degree in cultured hippocampal neurons and a human GluR2(flip/unedited) cell line (IC(50): 433 and 596 muM, respectively) and at higher concentrations, kynA also inhibited the strychnine-sensitive glycine receptor ( approximately 35% inhibition by 3 mM kynA). Interestingly, kynA inhibited the peak amplitude (IC(50): 2.9 mM for 10 muM GABA) and slowed the decay kinetics of GABA-evoked currents in cultured neurons. In contrast, we found that kynA (1-3 mM) had no effect on ACh-evoked, methyllycaconitine (MLA)-sensitive currents in a human alpha7 nicotinic receptor (nAChR) cell line, rat hippocampal neurons in primary culture or CA1 stratum radiatum interneurons in rat brain slices. However, DMSO (>1%) did inhibit alpha7 nAChR-mediated currents. In conclusion, kynA is an antagonist at NMDA, AMPA and glycine receptors and a modulator of GABA(A) receptors, but we find no evidence for any effect of kynA at the alpha7 nAChR.
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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/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Kynurenic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic,
http://linkedlifedata.com/resource/pubmed/chemical/alpha7 nicotinic acetylcholine...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1873-7064
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
57
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
242-9
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pubmed:dateRevised |
2010-6-4
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pubmed:meshHeading |
pubmed-meshheading:19523966-Animals,
pubmed-meshheading:19523966-Brain,
pubmed-meshheading:19523966-Cell Line,
pubmed-meshheading:19523966-Cells, Cultured,
pubmed-meshheading:19523966-Excitatory Amino Acid Antagonists,
pubmed-meshheading:19523966-Hippocampus,
pubmed-meshheading:19523966-Humans,
pubmed-meshheading:19523966-Ion Channel Gating,
pubmed-meshheading:19523966-Ion Channels,
pubmed-meshheading:19523966-Kinetics,
pubmed-meshheading:19523966-Kynurenic Acid,
pubmed-meshheading:19523966-Neurons,
pubmed-meshheading:19523966-Patch-Clamp Techniques,
pubmed-meshheading:19523966-Rats,
pubmed-meshheading:19523966-Rats, Sprague-Dawley,
pubmed-meshheading:19523966-Receptors, AMPA,
pubmed-meshheading:19523966-Receptors, GABA-A,
pubmed-meshheading:19523966-Receptors, Glycine,
pubmed-meshheading:19523966-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:19523966-Receptors, Nicotinic
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pubmed:year |
2009
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pubmed:articleTitle |
Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels.
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pubmed:affiliation |
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom. selina.mok@gsk.com
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pubmed:publicationType |
Journal Article,
In Vitro
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