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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1995-1-24
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pubmed:abstractText |
Exposure of mesencephalic dopamine neurons to an irreversible inhibitor of succinate dehydrogenase (SDH), 3-nitropropionic acid (3-NPA), for 24 h on day 12 in vitro, produced a dose-dependent loss of high-affinity dopamine uptake when measured 48 h following 3-NPA removal. ATP concentrations in the cultures were reduced by 57% after 3 h of treatment with the highest concentration of 3-NPA tested (500 microM). To determine whether glutamate receptors mediated the dopamine toxicity by 3-NPA, cultures were examined for their sensitivity to excitatory amino acid-induced toxicity. Mesencephalic cultures exposed to either 100 microM NMDA or kainate, on day 12 for 24 h, showed complete loss of dopamine uptake following 48 h of recovery. The NMDA and non-NMDA antagonists, MK-801 (1 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 15 microM), completely prevented the effects of NMDA or kainate, respectively, when present at the time of toxin exposure. In cultures treated with 3-NPA, MK-801, but not CNQX, significantly attenuated the loss of dopamine uptake. Direct measurement of the effect of 3-NPA on SDH activity showed that 3-NPA dose-dependently inhibited SDH in vitro in a manner commensurate with the loss of dopamine uptake by 3-NPA. MK-801 had no effect on basal SDH activity or on 3-NPA inhibition of SDH. These data are consistent with the interpretation that metabolic inhibition in dopamine neurons can trigger a secondary excitotoxicity that is mediated by NMDA receptors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/6-Cyano-7-nitroquinoxaline-2,3-dione,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antihypertensive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Succinate Dehydrogenase
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
455-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7798946-6-Cyano-7-nitroquinoxaline-2,3-dione,
pubmed-meshheading:7798946-Adenosine Triphosphate,
pubmed-meshheading:7798946-Animals,
pubmed-meshheading:7798946-Antihypertensive Agents,
pubmed-meshheading:7798946-Cells, Cultured,
pubmed-meshheading:7798946-Dizocilpine Maleate,
pubmed-meshheading:7798946-Dopamine,
pubmed-meshheading:7798946-Mesencephalon,
pubmed-meshheading:7798946-N-Methylaspartate,
pubmed-meshheading:7798946-Neurons,
pubmed-meshheading:7798946-Nitro Compounds,
pubmed-meshheading:7798946-Propionic Acids,
pubmed-meshheading:7798946-Rats,
pubmed-meshheading:7798946-Rats, Sprague-Dawley,
pubmed-meshheading:7798946-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:7798946-Succinate Dehydrogenase
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pubmed:year |
1995
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pubmed:articleTitle |
NMDA receptor involvement in toxicity to dopamine neurons in vitro caused by the succinate dehydrogenase inhibitor 3-nitropropionic acid.
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pubmed:affiliation |
Department of Neurology, University of Medicine and Dentistry of NJ-Robert Wood Johnson Medical School, Piscataway 08854.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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