Relationship between susceptibility to dmcm-induced generalized motor convulsions and low-affinity [h-3]-ouabain binding in membranes in rat brain

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dc.contributor.author Contó, Marcos Brandao [UNIFESP]
dc.contributor.author Campana Venditti, Marco Antonio [UNIFESP]
dc.date.accessioned 2019-01-21T10:29:27Z
dc.date.available 2019-01-21T10:29:27Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.2174/1874467209666160408152558
dc.identifier.citation Current Molecular Pharmacology. Sharjah, v. 9, n. 4, p. 332-336, 2016.
dc.identifier.issn 1874-4672
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/49227
dc.description.abstract Background and Objective: Epilepsy is one of the most prevalent neurological disorders worldwide, but its underlying mechanisms have not yet been clarified. Among the possible molecular mechanisms that underlie its occurrence are those that are responsible for the neuronal ionic gradient, including the transmembrane enzyme Na+, K+-adenosine triphosphatase (ATPase). Na+, K+-ATPase plays an important role in controlling neuronal excitability, and it is believed to be related to the pathophysiology of epilepsy. However, the specific isozymes that may be related to this neurological disorder remain to be determined. The 3 subunit-containing Na+, K+-ATPase isozyme has high affinity for ouabain and appears to play a major role in the pathogenesis of epilepsies. However, more studies are needed to evaluate the possible participation of Na+, K(+)ATPase isozymes with lower affinity for ouabain (i.e., those that contain the 1 and 2 subunits). Methods: The present study investigated whether rats with high (HTR) and low (LTR) thresholds for clonic convulsions that are induced by a benzodiazepine inverse agonist differ in the binding of [H-3]ouabain to Na+, K+-ATPase isozymes with lower affinity to ouabain in discrete brain regions. Results: Compared with the HTR group, the LTR group exhibited lower binding of [H-3]-ouabain in the brainstem and frontal cortex. Conclusion: This finding supports the hypothesis that epilepsy is associated with impairments in Na+, K(+)ATPase activity. The results also suggest that Na+, K+-ATPase isozymes that contain the 1/2 subunits in these brain regions may underlie the susceptibility to methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced convulsions. en
dc.description.sponsorship Associacao Fundo de Incentivo a Pesquisa (AFIP)
dc.description.sponsorship Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.format.extent 332-336
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof Current Molecular Pharmacology
dc.rights Acesso restrito
dc.subject Benzodiazepine Inverse Agonist en
dc.subject Epilepsy en
dc.subject Generalized Motor Convulsions en
dc.subject Low-Affinity [H-3]-ouabain Binding en
dc.subject Na+,K+-Atpase Isozymes en
dc.subject Ouabain en
dc.subject SeizuresK+-Atpase Activity en
dc.subject Ouabain Binding en
dc.subject Quantitative Autoradiography en
dc.subject Alpha-3 Isoforms en
dc.subject Sodium-Pump en
dc.subject Na+ en
dc.subject Seizures en
dc.subject Mice en
dc.subject Hippocampus en
dc.subject Thresholds en
dc.title Relationship between susceptibility to dmcm-induced generalized motor convulsions and low-affinity [h-3]-ouabain binding in membranes in rat brain en
dc.type Artigo
dc.description.affiliation Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/ EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP 04023-062, Brazil
dc.description.affiliationUnifesp Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/ EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP 04023-062, Brazil
dc.description.sponsorshipID Contó, Marcos Brandao [UNIFESP]
dc.description.sponsorshipID Venditti, Marco Antonio Campana [UNIFESP]
dc.identifier.doi 10.2174/1874467209666160408152558
dc.description.source Web of Science
dc.identifier.wos WOS:000406220600008



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