Source:http://linkedlifedata.com/resource/pubmed/id/19162139
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2009-3-3
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| pubmed:abstractText |
The major aim of this study was to elucidate the relationship between nitric oxide (NO) and generalized epilepsy. Mice lacking the neuronal nitric oxide synthase (nNOS) gene (nNOS(-/-)) were used in this study to determine the relationship between nNOS alpha and NO in pentylentetrazole (PTZ)-induced convulsions. nNOS(-/-) mice exhibited severe convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg i.p.) and convulsive doses were lethal in all of the mice (60 mg/kg i.p.) following tonic convulsions. The results were confirmed by using selective nNOS inhibitors in wild-type (nNOS(+/+)) mice. The higher doses of the nNOS inhibitors 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) and 3-bromo-7-nitroindazole (3Br7NI) inhibited clonic-tonic convulsions induced by a convulsive dose of PTZ (60 mg/kg) in nNOS(+/+) mice. In contrast, either TRIM or 3Br7NI at lower doses enhanced convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg) in nNOS(+/+) mice similar to nNOS(-/-) mice treated with PTZ. Such a proconvulsant effect was observed in nNOS(+/+) mice pretreated with nNOS inhibitors but not other NOS inhibitors. These results indicate that NO may be regarded as an anticonvulsant or a proconvulsant substance in relation to convulsions induced by PTZ in mice. Pretreatment with N-methyl-d-aspartate (NMDA) receptor antagonists (5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), (E)-(+/-)-2-amino-4-methyl-5-phospho no-3-pentenoic acid ethyl ester, CGP39551) and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) inhibited a subconvulsive dose of PTZ-induced convulsions in nNOS(-/-) mice, demonstrating that convulsions induced by PTZ are modulated by endogenous NO production and ionotropic glutamate receptor-mediated stimulation. These results suggest a negative or positive modulation of neuronal interactions by basal or enhanced NO production, respectively.
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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/1-(2-trifluoromethylphenyl)imidazole,
http://linkedlifedata.com/resource/pubmed/chemical/2,3-dioxo-6-nitro-7-sulfamoylbenzo(f...,
http://linkedlifedata.com/resource/pubmed/chemical/3-bromo-7-nitroindazole,
http://linkedlifedata.com/resource/pubmed/chemical/Convulsants,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Indazoles,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Nos1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pentylenetetrazole,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0306-4522
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
17
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| pubmed:volume |
159
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
735-43
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| pubmed:meshHeading |
pubmed-meshheading:19162139-Animals,
pubmed-meshheading:19162139-Convulsants,
pubmed-meshheading:19162139-Disease Models, Animal,
pubmed-meshheading:19162139-Dizocilpine Maleate,
pubmed-meshheading:19162139-Dose-Response Relationship, Drug,
pubmed-meshheading:19162139-Gene Expression Regulation,
pubmed-meshheading:19162139-Imidazoles,
pubmed-meshheading:19162139-Indazoles,
pubmed-meshheading:19162139-Mice,
pubmed-meshheading:19162139-Mice, Inbred C57BL,
pubmed-meshheading:19162139-Mice, Knockout,
pubmed-meshheading:19162139-N-Methylaspartate,
pubmed-meshheading:19162139-Neuroprotective Agents,
pubmed-meshheading:19162139-Nitric Oxide,
pubmed-meshheading:19162139-Nitric Oxide Synthase Type I,
pubmed-meshheading:19162139-Pentylenetetrazole,
pubmed-meshheading:19162139-Quinoxalines,
pubmed-meshheading:19162139-Seizures
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| pubmed:year |
2009
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| pubmed:articleTitle |
Paradoxical facilitation of pentylenetetrazole-induced convulsion susceptibility in mice lacking neuronal nitric oxide synthase.
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| pubmed:affiliation |
Laboratory for Brain Science, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki-City, Kagawa 769-2193, Japan. itoh@kph.bunri-u.ac.jp
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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