Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors

Autores
Beltrán González, Andrea Natalia; Lopez Pazos, Manuel Ignacio; Calvo, Daniel Juan
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Histamine may exert its effects not only through its canonical (G-protein coupled) receptors, but also by other mechanisms which are currently being studied. It was shown that histamine can modulate the activity of different ligand-gated ion channels including several subtypes of GABAA receptors. For example, it gates homomeric GABAAβ2-3 and acts as a positive modulator on heteromeric GABAAα1-5β2γ2 receptors, but its effects on GABAAρ1 receptors had never been studied before. We previously reported that histamine inhibited GABAAρ1 receptor responses in a dose-dependent, reversible and voltage-independent manner. This was the first evidence of histamine mediating an inhibitory action on a ionotropic GABA receptor and contributed to explore the role of histamine in the retina. In the present study we analyzed the mechanism of action involved in this modulation. GABAAρ1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp. Dose-response curves for GABA performed in the presence of histamine were shifted to the right, with no changes in the slope, nHill or maximum response. No use dependent effects were observed. These results are compatible with a competitive antagonism operating on the GABAAρ1 receptors. Computational docking studies and single-oocyte binding assays with tritiated GABA are being conducted to confirm the mechanism of action proposed here.
Fil: Beltrán González, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lopez Pazos, Manuel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Córdoba
Argentina
Sociedad Argentina de Investigaciones en Neurociencias
Materia
GABAA RECEPTOR
HISTAMINE
GABARHO1 RECEPTOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/243016
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptorsBeltrán González, Andrea NataliaLopez Pazos, Manuel IgnacioCalvo, Daniel JuanGABAA RECEPTORHISTAMINEGABARHO1 RECEPTORhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Histamine may exert its effects not only through its canonical (G-protein coupled) receptors, but also by other mechanisms which are currently being studied. It was shown that histamine can modulate the activity of different ligand-gated ion channels including several subtypes of GABAA receptors. For example, it gates homomeric GABAAβ2-3 and acts as a positive modulator on heteromeric GABAAα1-5β2γ2 receptors, but its effects on GABAAρ1 receptors had never been studied before. We previously reported that histamine inhibited GABAAρ1 receptor responses in a dose-dependent, reversible and voltage-independent manner. This was the first evidence of histamine mediating an inhibitory action on a ionotropic GABA receptor and contributed to explore the role of histamine in the retina. In the present study we analyzed the mechanism of action involved in this modulation. GABAAρ1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp. Dose-response curves for GABA performed in the presence of histamine were shifted to the right, with no changes in the slope, nHill or maximum response. No use dependent effects were observed. These results are compatible with a competitive antagonism operating on the GABAAρ1 receptors. Computational docking studies and single-oocyte binding assays with tritiated GABA are being conducted to confirm the mechanism of action proposed here.Fil: Beltrán González, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lopez Pazos, Manuel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaXXXIII Congreso Anual de la Sociedad Argentina de Investigación en NeurocienciasCórdobaArgentinaSociedad Argentina de Investigaciones en NeurocienciasSociedad Argentina de Investigaciones en Neurociencias2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/243016Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Córdoba; Argentina; 2018; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/wp-content/uploads/2022/01/SAN2018_Cordoba-UNC_libro-de-resumenes.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:35:56Zoai:ri.conicet.gov.ar:11336/243016instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:35:56.758CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
title Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
spellingShingle Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
Beltrán González, Andrea Natalia
GABAA RECEPTOR
HISTAMINE
GABARHO1 RECEPTOR
title_short Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
title_full Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
title_fullStr Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
title_full_unstemmed Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
title_sort Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors
dc.creator.none.fl_str_mv Beltrán González, Andrea Natalia
Lopez Pazos, Manuel Ignacio
Calvo, Daniel Juan
author Beltrán González, Andrea Natalia
author_facet Beltrán González, Andrea Natalia
Lopez Pazos, Manuel Ignacio
Calvo, Daniel Juan
author_role author
author2 Lopez Pazos, Manuel Ignacio
Calvo, Daniel Juan
author2_role author
author
dc.subject.none.fl_str_mv GABAA RECEPTOR
HISTAMINE
GABARHO1 RECEPTOR
topic GABAA RECEPTOR
HISTAMINE
GABARHO1 RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Histamine may exert its effects not only through its canonical (G-protein coupled) receptors, but also by other mechanisms which are currently being studied. It was shown that histamine can modulate the activity of different ligand-gated ion channels including several subtypes of GABAA receptors. For example, it gates homomeric GABAAβ2-3 and acts as a positive modulator on heteromeric GABAAα1-5β2γ2 receptors, but its effects on GABAAρ1 receptors had never been studied before. We previously reported that histamine inhibited GABAAρ1 receptor responses in a dose-dependent, reversible and voltage-independent manner. This was the first evidence of histamine mediating an inhibitory action on a ionotropic GABA receptor and contributed to explore the role of histamine in the retina. In the present study we analyzed the mechanism of action involved in this modulation. GABAAρ1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp. Dose-response curves for GABA performed in the presence of histamine were shifted to the right, with no changes in the slope, nHill or maximum response. No use dependent effects were observed. These results are compatible with a competitive antagonism operating on the GABAAρ1 receptors. Computational docking studies and single-oocyte binding assays with tritiated GABA are being conducted to confirm the mechanism of action proposed here.
Fil: Beltrán González, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lopez Pazos, Manuel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Córdoba
Argentina
Sociedad Argentina de Investigaciones en Neurociencias
description Histamine may exert its effects not only through its canonical (G-protein coupled) receptors, but also by other mechanisms which are currently being studied. It was shown that histamine can modulate the activity of different ligand-gated ion channels including several subtypes of GABAA receptors. For example, it gates homomeric GABAAβ2-3 and acts as a positive modulator on heteromeric GABAAα1-5β2γ2 receptors, but its effects on GABAAρ1 receptors had never been studied before. We previously reported that histamine inhibited GABAAρ1 receptor responses in a dose-dependent, reversible and voltage-independent manner. This was the first evidence of histamine mediating an inhibitory action on a ionotropic GABA receptor and contributed to explore the role of histamine in the retina. In the present study we analyzed the mechanism of action involved in this modulation. GABAAρ1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp. Dose-response curves for GABA performed in the presence of histamine were shifted to the right, with no changes in the slope, nHill or maximum response. No use dependent effects were observed. These results are compatible with a competitive antagonism operating on the GABAAρ1 receptors. Computational docking studies and single-oocyte binding assays with tritiated GABA are being conducted to confirm the mechanism of action proposed here.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/243016
Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Córdoba; Argentina; 2018; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243016
identifier_str_mv Characterization of the antagonistic actions of histamine on homomeric GABAArho1 receptors; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Córdoba; Argentina; 2018; 1-1
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/wp-content/uploads/2022/01/SAN2018_Cordoba-UNC_libro-de-resumenes.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Neurociencias
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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