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dc.contributor.authorKosenko, Elena
dc.contributor.authorLlansola, Marta
dc.contributor.authorMontoliu, Carmina
dc.contributor.authorMonfort, Pilar
dc.contributor.authorRodrigo, Regina
dc.contributor.authorHernández Viadel, Mariluz
dc.contributor.authorErceg, Slaven
dc.contributor.authorSánchez Pérez, Ana María
dc.contributor.authorFelipo, Vicente
dc.date.accessioned2017-02-20T08:23:15Z
dc.date.available2017-02-20T08:23:15Z
dc.date.issued2003-09
dc.identifier.citationKOSENKO, Elena; LLANSOLA, Marta; MONTOLIU, Carmina; MONFORT, Pilar; RODRIGO, Regina; HERNÁNDEZ VIADEL, Mariluz; ERCEG, Slaven; SÁNCHEZ PÉREZ, Ana María; FELIPO, Vicente. Glutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxide. Neurochemistry International (2003), v. 43, issues 4-5, pp. 493-499ca_CA
dc.identifier.urihttp://hdl.handle.net/10234/166163
dc.description.abstractAcute intoxication with large doses of ammonia leads to rapid death. The main mechanism for ammonia elimination in brain is its reaction with glutamate to form glutamine. This reaction is catalyzed by glutamine synthetase and consumes ATP. In the course of studies on the molecular mechanism of acute ammonia toxicity, we have found that glutamine synthetase activity and glutamine content in brain are modulated by NMDA receptors and nitric oxide. The main findings can be summarized as follows. Blocking NMDA receptors prevents ammonia-induced depletion of brain ATP and death of rats but not the increase in brain glutamine, indicating that ammonia toxicity is not due to increased activity of glutamine synthetase or formation of glutamine but to excessive activation of NMDA receptors. Blocking NMDA receptors in vivo increases glutamine synthetase activity and glutamine content in brain, indicating that tonic activation of NMDA receptors maintains a tonic inhibition of glutamine synthetase. Blocking NMDA receptors in vivo increases the activity of glutamine synthetase assayed in vitro, indicating that increased activity is due to a covalent modification of the enzyme. Nitric oxide inhibits glutamine synthetase, indicating that the covalent modification that inhibits glutamine synthetase is a nitrosylation or a nitration. Inhibition of nitric oxide synthase increases the activity of glutamine synthetase, indicating that the covalent modification is reversible and it must be an enzyme that denitrosylate or denitrate glutamine synthetase. NMDA mediated activation of nitric oxide synthase is responsible only for part of the tonic inhibition of glutamine synthetase. Other sources of nitric oxide are also contributing to this tonic inhibition. Glutamine synthetase is not working at maximum rate in brain and its activity may be increased pharmacologically by manipulating NMDA receptors or nitric oxide content. This may be useful, for example, to increase ammonia detoxification in brain in hyperammonemic situations.ca_CA
dc.description.sponsorShipSupported in part by grants from the Spanish Plan Nacional de I + D (SAF97-0001) and of the Promoción General del Conocimiento of Ministerio de Educación y Cultura (PM99-0019).ca_CA
dc.format.extent17 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherElsevierca_CA
dc.relation.isPartOfNeurochemistry International (2003), v. 43, issues 4-5ca_CA
dc.subjectGlutamine synthetaseca_CA
dc.subjectBrain glutamineca_CA
dc.subjectNMDA receptorsca_CA
dc.subjectNitric oxideca_CA
dc.subjectHyperammonemiaca_CA
dc.subjectHepatic encephalopathyca_CA
dc.titleGlutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxideca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1016/S0197-0186(03)00039-1
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_CA
dc.relation.publisherVersionhttp://www.sciencedirect.com/science/article/pii/S0197018603000391ca_CA


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