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dc.contributor.author Andrea Beltrán González
dc.contributor.author Pomata, Pablo Ernesto
dc.contributor.author Goutman, Juan Diego
dc.contributor.author Gasulla, Javier
dc.contributor.author Chebib, Mary
dc.contributor.author Calvo, Daniel Juan
dc.date.available 2016-02-01T20:29:36Z
dc.date.issued 2014-09-22
dc.identifier.citation Andrea Beltrán González; Pomata, Pablo Ernesto; Goutman, Juan Diego; Gasulla, Javier; Chebib, Mary; et al.; Benzodiazepine modulation of homomeric GABAAρ1 receptors: Differential effects of diazepam and 40´-chlorodiazepam; Elsevier; European Journal of Pharmacology; 743; 22-9-2014; 24-30
dc.identifier.issn 0014-2999
dc.identifier.uri http://hdl.handle.net/11336/3944
dc.description.abstract GABAA receptors (GABAARs) are ligand-gated ion channels that mediate inhibitory neurotransmission in the central nervous system (CNS). They are members of the Cys-loop receptor family and display marked structural and functional heterogeneity. Many GABAARs receptor subtypes are allosterically modulated by benzodiazepines (BDZs), which are drugs extensively used as anxiolytics, sedative-hypnotics and anticonvulsants. One high-affinity site and at least three additional low-affinity sites for BDZ recognition have been identified in several heteromeric and homomeric variants of the GABAARs (e.g.: alpha1-beta2-gamma2, alpha1beta2/3, beta3, etc.). However, the modulation of homomeric GABAArhoRs by BDZs was not previously revealed, and these receptors, for a long a time, were assumed to be fully insensitive to the actions of these drugs. In the present study, human homomeric GABAArho1 receptors were expressed in Xenopus oocytes and GABA-evoked responses electrophysiologically recorded in the presence or absence of BDZs. GABAArho1 receptor-mediated responses were modulated by diazepam and 4´-chlorodiazepam in the micromolar range, in a concentration-dependent, voltage-independent and reversible manner. Diazepam produced potentiating effects on GABA-evoked Cl(-) currents and 4´-Cl diazepam induced biphasic effects depending on the GABA concentration, whereas Ro15-4513 and alprazolam were negative modulators. BDZ actions were insensitive to flumazenil. Other BDZs showed negligible activity at equivalent experimental conditions. Our results suggest that GABAArho1 receptor function can be selectively and differentially modulated by BDZs.
dc.format application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject GABA receptors
dc.subject Cys-loop receptors
dc.subject Benzodiazepines
dc.subject Bicuculline-insensitive GABA receptors
dc.subject.classification Neurociencias
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Benzodiazepine modulation of homomeric GABAAρ1 receptors: Differential effects of diazepam and 40´-chlorodiazepam
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2016-03-30 10:35:44.97925-03
dc.journal.volume 743
dc.journal.pagination 24-30
dc.journal.pais Países Bajos
dc.journal.ciudad Amsterdam
dc.description.fil Fil: Andrea Beltrán González. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil Fil: Pomata, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil Fil: Goutman, Juan Diego. 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: Chebib, Mary. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología 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/S001429991400661X
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ejphar.2014.09.017
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/ark/0014-2999


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)