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dc.contributor.author
Calero, Cecilia Ines
dc.contributor.author
Beltrán González, Andrea Natalia
dc.contributor.author
Gasulla, Javier
dc.contributor.author
Alvarez, Silvia
dc.contributor.author
Evelson, Pablo Andres
dc.contributor.author
Calvo, Daniel Juan
dc.date.available
2016-07-19T19:26:37Z
dc.date.issued
2013-08
dc.identifier.citation
Calero, Cecilia Ines; Beltrán González, Andrea Natalia; Gasulla, Javier; Alvarez, Silvia; Evelson, Pablo Andres; et al.; Quercetin antagonism of GABAAρ1 receptors is prevented by ascorbic acid through a redox-independent mechanism; Elsevier; European Journal of Pharmacology; 714; 1-3; 8-2013; 274-280
dc.identifier.issn
0014-2999
dc.identifier.uri
http://hdl.handle.net/11336/6601
dc.description.abstract
Quercetin is a natural flavonoid widely distributed in plants that acts as a neuroprotective agent and modulates the activity of different synaptic receptors and ion channels, including the ionotropic GABA receptors. GABAArho1 receptors were shown to be antagonized by quercetin, but the mechanisms underlying these antagonistic actions are still unknown. We have analyzed here if the antagonistic action produced by quercetin on GABAArho1 receptors was related to its redox activity or due to alternative mechanism/s. Homomeric GABAArho1 receptors were expressed in frog oocytes and GABA-evoked responses electrophysiologically recorded. Quercetin effects on GABAArho1 receptors were examined in the absence or presence of ascorbic acid. Chemical protection of cysteines by selective sulfhydryl reagents and site directed mutagenesis experiments were also used to determine ρ₁ subunit residues involved in quercetin actions. Quercetin antagonized GABAArho1 receptor responses in a dose-dependent, fast and reversible manner. Quercetin inhibition was prevented in the presence of ascorbic acid, but not by thiol reagents that modify the extracellular Cys-loop of these receptors. H141, an aminoacidic residue located near to the rho1 subunit GABA binding site, was involved in the allosteric modulation of GABAArho1 receptors by several agents including ascorbic acid. Quercetin similarly antagonized GABA-evoked responses mediated by mutant (H141D)GABAArho1 and wild-type receptors, but prevention exerted by ascorbic acid on quercetin effects was impaired in mutant receptors. Taken together the present results suggest that quercetin antagonistic actions on GABAArho1 receptors are mediated through a redox-independent allosteric mechanism.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Gaba Receptor
dc.subject
Flavonoid
dc.subject
Quercetin
dc.subject
Ascorbic Acid
dc.subject
Allosteric Modulator
dc.subject.classification
Neurociencias
dc.subject.classification
Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Quercetin antagonism of GABAAρ1 receptors is prevented by ascorbic acid through a redox-independent mechanism
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-02-01T16:36:58Z
dc.journal.volume
714
dc.journal.number
1-3
dc.journal.pagination
274-280
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Beltrán González, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Gasulla, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina
dc.description.fil
Fil: Evelson, Pablo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina
dc.description.fil
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina
dc.journal.title
European Journal of Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014299913005669
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2013.07.044
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ejphar.2013.07.044
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