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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-7-27
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1873-7064
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
242-9
pubmed:dateRevised
2010-6-4
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
pubmed:year
2009
pubmed:articleTitle
Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels.
pubmed:affiliation
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom. selina.mok@gsk.com
pubmed:publicationType
Journal Article, In Vitro