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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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