Negative modulation of the GABAAρ1 receptor function by histamine

Autores
Beltrán González, Andrea N.; López Pazos, Manuel I.; Del Vas, Mariana; Calvo, Daniel Juan
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor.
Instituto de Biotecnología
Fil: Beltrán González, Andrea N. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Beltrán González, Andrea N. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: López Pazos, Manuel I. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: López Pazos, Manuel I. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Del Vas, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Del Vas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Calvo, Daniel J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Calvo, Daniel J. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fuente
European Journal of Pharmacology 955 : 175880. (September 2023)
Materia
Histamina
GABA
Neurotransmisores
Histamine
Gamma-aminobutyric Acid
Neurotransmitters
Ácido Gamma-aminobutírico
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/14787
Acceder
id INTADig_1a52ec7652a2337cf4e2403aa539a348
oai_identifier_str oai:localhost:20.500.12123/14787
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Negative modulation of the GABAAρ1 receptor function by histamineBeltrán González, Andrea N.López Pazos, Manuel I.Del Vas, MarianaCalvo, Daniel JuanHistaminaGABANeurotransmisoresHistamineGamma-aminobutyric AcidNeurotransmittersÁcido Gamma-aminobutíricoBesides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor.Instituto de BiotecnologíaFil: Beltrán González, Andrea N. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaFil: Beltrán González, Andrea N. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaFil: López Pazos, Manuel I. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaFil: López Pazos, Manuel I. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaFil: Del Vas, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Del Vas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calvo, Daniel J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaFil: Calvo, Daniel J. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; ArgentinaElsevier2023-07-20T14:20:37Z2023-07-20T14:20:37Z2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/14787https://www.sciencedirect.com/science/article/pii/S00142999230039161879-07120014-2999https://doi.org/10.1016/j.ejphar.2023.175880European Journal of Pharmacology 955 : 175880. (September 2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:46:00Zoai:localhost:20.500.12123/14787instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:46:01.111INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Negative modulation of the GABAAρ1 receptor function by histamine
title Negative modulation of the GABAAρ1 receptor function by histamine
spellingShingle Negative modulation of the GABAAρ1 receptor function by histamine
Beltrán González, Andrea N.
Histamina
GABA
Neurotransmisores
Histamine
Gamma-aminobutyric Acid
Neurotransmitters
Ácido Gamma-aminobutírico
title_short Negative modulation of the GABAAρ1 receptor function by histamine
title_full Negative modulation of the GABAAρ1 receptor function by histamine
title_fullStr Negative modulation of the GABAAρ1 receptor function by histamine
title_full_unstemmed Negative modulation of the GABAAρ1 receptor function by histamine
title_sort Negative modulation of the GABAAρ1 receptor function by histamine
dc.creator.none.fl_str_mv Beltrán González, Andrea N.
López Pazos, Manuel I.
Del Vas, Mariana
Calvo, Daniel Juan
author Beltrán González, Andrea N.
author_facet Beltrán González, Andrea N.
López Pazos, Manuel I.
Del Vas, Mariana
Calvo, Daniel Juan
author_role author
author2 López Pazos, Manuel I.
Del Vas, Mariana
Calvo, Daniel Juan
author2_role author
author
author
dc.subject.none.fl_str_mv Histamina
GABA
Neurotransmisores
Histamine
Gamma-aminobutyric Acid
Neurotransmitters
Ácido Gamma-aminobutírico
topic Histamina
GABA
Neurotransmisores
Histamine
Gamma-aminobutyric Acid
Neurotransmitters
Ácido Gamma-aminobutírico
dc.description.none.fl_txt_mv Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor.
Instituto de Biotecnología
Fil: Beltrán González, Andrea N. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Beltrán González, Andrea N. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: López Pazos, Manuel I. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: López Pazos, Manuel I. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Del Vas, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Del Vas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Calvo, Daniel J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
Fil: Calvo, Daniel J. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina
description Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-20T14:20:37Z
2023-07-20T14:20:37Z
2023-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/14787
https://www.sciencedirect.com/science/article/pii/S0014299923003916
1879-0712
0014-2999
https://doi.org/10.1016/j.ejphar.2023.175880
url http://hdl.handle.net/20.500.12123/14787
https://www.sciencedirect.com/science/article/pii/S0014299923003916
https://doi.org/10.1016/j.ejphar.2023.175880
identifier_str_mv 1879-0712
0014-2999
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv European Journal of Pharmacology 955 : 175880. (September 2023)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1844619177133867008
score 12.559606

Publicaciones similares