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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-3-2
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pubmed:abstractText |
In cerebellar neurons in culture, activation of group I metabotropic glutamate receptors (mGluRs) prevents glutamate and NMDA-induced neuronal death, indicating that it interferes with the excitotoxic mechanisms leading to death. However, it is not known which step of these mechanisms is affected by mGluRs. The aims of this work were to assess: (a) whether activation of group I mGluRs (mGluR1 or mGluR5) impairs NMDA-induced activation of the glutamate-nitric oxide-cGMP pathway; (b) which mGluR (1 or 5) is responsible for this impairment and (c) whether impairment of the pathway occurs at the level of activation of soluble guanylate cyclase by nitric oxide or of activation of neuronal nitric oxide synthase (nNOS) by NMDA. It is shown that activation of mGluR1 enhances the function of the glutamate-nitric oxide-cGMP pathway by increasing activation of soluble guanylate cyclase by nitric oxide. In contrast, mGluR5 activation inhibits the glutamate-nitric oxide-cGMP pathway by reducing NMDA-induced activation of nNOS. This is due to reduced NMDA-induced increase in cAMP, reduced activation of Akt by cAMP and of nNOS by Akt. The impairment of activation of the glutamate-NO-cGMP pathway by activation of mGluR5 would contribute to its neuroprotective effect against excitotoxicity in cerebellar neurons in culture.
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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/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Citrulline,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/metabotropic glutamate receptor 5,
http://linkedlifedata.com/resource/pubmed/chemical/metabotropic glutamate receptor...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1872-9754
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2009 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
535-45
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pubmed:meshHeading |
pubmed-meshheading:20043967-Animals,
pubmed-meshheading:20043967-Arginine,
pubmed-meshheading:20043967-Blotting, Western,
pubmed-meshheading:20043967-Calcium,
pubmed-meshheading:20043967-Cells, Cultured,
pubmed-meshheading:20043967-Cerebellum,
pubmed-meshheading:20043967-Citrulline,
pubmed-meshheading:20043967-Cyclic AMP,
pubmed-meshheading:20043967-Cyclic GMP,
pubmed-meshheading:20043967-Enzyme Activation,
pubmed-meshheading:20043967-Excitatory Amino Acid Agonists,
pubmed-meshheading:20043967-Guanylate Cyclase,
pubmed-meshheading:20043967-N-Methylaspartate,
pubmed-meshheading:20043967-Neurons,
pubmed-meshheading:20043967-Nitrates,
pubmed-meshheading:20043967-Nitric Oxide Synthase Type I,
pubmed-meshheading:20043967-Nitrites,
pubmed-meshheading:20043967-Oncogene Protein v-akt,
pubmed-meshheading:20043967-Rats,
pubmed-meshheading:20043967-Rats, Wistar,
pubmed-meshheading:20043967-Receptors, Metabotropic Glutamate,
pubmed-meshheading:20043967-Receptors, N-Methyl-D-Aspartate
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pubmed:year |
2010
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pubmed:articleTitle |
Metabotropic glutamate receptor 5, but not 1, modulates NMDA receptor-mediated activation of neuronal nitric oxide synthase.
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pubmed:affiliation |
Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, 46012 Valencia, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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