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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2001-4-20
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pubmed:abstractText |
The glutamate analog (+/-) threo-3-methylglutamate (T3MG) has recently been reported to inhibit the EAAT2 but not EAAT1 subtype of high-affinity, Na(+)-dependent excitatory amino acid transporter (EAAT). We have examined the effects of T3MG on glutamate-elicited currents mediated by EAATs 1-4 expressed in Xenopus oocytes and on the transport of radiolabeled substrate in mammalian cell lines expressing EAATs 1-3. T3MG was found to be an inhibitor of EAAT2 and EAAT4 but a weak inhibitor of EAAT1 and EAAT3. T3MG competitively inhibited uptake of D-[(3)H]-aspartate into both cortical and cerebellar synaptosomes with a similar potency, consistent with its inhibitory activity on the cloned EAAT2 and EAAT4 subtypes. In addition, T3MG produced substrate-like currents in oocytes expressing EAAT4 but not EAAT2. However, T3MG was unable to elicit heteroexchange of preloaded D-[(3)H]-aspartate in cerebellar synaptosomes, inconsistent with the behavior of a substrate inhibitor. Finally, T3MG acts as a poor ionotropic glutamate receptor agonist in cultured hippocampal neurons: concentrations greater than 100 microM T3MG were required to elicit significant NMDA receptor-mediated currents. Thus, T3MG represents a pharmacological tool for the study of not only the predominant EAAT2 subtype but also the EAAT4 subtype highly expressed in cerebellum.
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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/2,3-dioxo-6-nitro-7-sulfamoylbenzo(f...,
http://linkedlifedata.com/resource/pubmed/chemical/2-Amino-5-phosphonovalerate,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Transport System X-AG,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Transporter 2,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Transporter 3,
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/Neurotransmitter Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurotransmitter,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Slc1a1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Slc1a2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Slc1a3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Slc1a6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
550-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11299317-2-Amino-5-phosphonovalerate,
pubmed-meshheading:11299317-ATP-Binding Cassette Transporters,
pubmed-meshheading:11299317-Action Potentials,
pubmed-meshheading:11299317-Amino Acid Transport System X-AG,
pubmed-meshheading:11299317-Animals,
pubmed-meshheading:11299317-Aspartic Acid,
pubmed-meshheading:11299317-Carrier Proteins,
pubmed-meshheading:11299317-Cell Line,
pubmed-meshheading:11299317-Cerebellum,
pubmed-meshheading:11299317-Cerebral Cortex,
pubmed-meshheading:11299317-Dogs,
pubmed-meshheading:11299317-Excitatory Amino Acid Transporter 1,
pubmed-meshheading:11299317-Excitatory Amino Acid Transporter 2,
pubmed-meshheading:11299317-Excitatory Amino Acid Transporter 3,
pubmed-meshheading:11299317-Excitatory Amino Acid Transporter 4,
pubmed-meshheading:11299317-Glutamate Plasma Membrane Transport Proteins,
pubmed-meshheading:11299317-Glutamic Acid,
pubmed-meshheading:11299317-Hippocampus,
pubmed-meshheading:11299317-Kidney,
pubmed-meshheading:11299317-Kinetics,
pubmed-meshheading:11299317-Neurotransmitter Uptake Inhibitors,
pubmed-meshheading:11299317-Oocytes,
pubmed-meshheading:11299317-Quinoxalines,
pubmed-meshheading:11299317-Rats,
pubmed-meshheading:11299317-Rats, Sprague-Dawley,
pubmed-meshheading:11299317-Receptors, Glutamate,
pubmed-meshheading:11299317-Receptors, Neurotransmitter,
pubmed-meshheading:11299317-Recombinant Fusion Proteins,
pubmed-meshheading:11299317-Symporters,
pubmed-meshheading:11299317-Synaptosomes,
pubmed-meshheading:11299317-Xenopus laevis
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pubmed:year |
2001
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pubmed:articleTitle |
Pharmacological characterization of threo-3-methylglutamic acid with excitatory amino acid transporters in native and recombinant systems.
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pubmed:affiliation |
Neurocrine Biosciences Inc., San Diego, California, USA Wyeth Neuroscience, Wyeth-Ayerst Research, Princeton, New Jersey, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study
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