Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol

Autores
Chrestia, Juan Facundo; Esandi, María del Carmen; Bouzat, Cecilia Beatriz
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. The aim of this work is to study α7 as one of the therapeutic targets of CBD in order to determine the mechanism by which the phytocannabinoid exerts its effect on the receptor. Wild-type and mutant α7 receptors were expressed in mammalian cells. To evaluate receptor ionotropic function, high-resolution single channel recordings in cell-attached and inside-out patch configurations were used. Changes in intracellular calcium levels were measured by confocal microscopy. We here reveal that CBD modulates α7 ionotropic and metabotropic functions. CBD leads to a concentration-dependent decrease of α7 single-channel activity with an IC50 of 0.54 ± 0.13 µM. The inhibition of α7 activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 conformational states. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 activation, thus decreasing cell calcium responses. The modulation of α7 is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.
Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Esandi, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Sociedad Franco-Argentina de Inmunología
Materia
NICOTINIC RECEPTORS
CANNABIDIOL
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:11336/228263
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiolChrestia, Juan FacundoEsandi, María del CarmenBouzat, Cecilia BeatrizNICOTINIC RECEPTORSCANNABIDIOLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. The aim of this work is to study α7 as one of the therapeutic targets of CBD in order to determine the mechanism by which the phytocannabinoid exerts its effect on the receptor. Wild-type and mutant α7 receptors were expressed in mammalian cells. To evaluate receptor ionotropic function, high-resolution single channel recordings in cell-attached and inside-out patch configurations were used. Changes in intracellular calcium levels were measured by confocal microscopy. We here reveal that CBD modulates α7 ionotropic and metabotropic functions. CBD leads to a concentration-dependent decrease of α7 single-channel activity with an IC50 of 0.54 ± 0.13 µM. The inhibition of α7 activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 conformational states. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 activation, thus decreasing cell calcium responses. The modulation of α7 is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Esandi, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaSociedad Franco-Argentina de InmunologíaFundación Revista Medicina2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228263Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 224-2240025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:37Zoai:ri.conicet.gov.ar:11336/228263instacron: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:34982025-09-03 09:44:37.86CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
title Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
spellingShingle Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
Chrestia, Juan Facundo
NICOTINIC RECEPTORS
CANNABIDIOL
title_short Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
title_full Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
title_fullStr Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
title_full_unstemmed Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
title_sort Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol
dc.creator.none.fl_str_mv Chrestia, Juan Facundo
Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author Chrestia, Juan Facundo
author_facet Chrestia, Juan Facundo
Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author_role author
author2 Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv NICOTINIC RECEPTORS
CANNABIDIOL
topic NICOTINIC RECEPTORS
CANNABIDIOL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. The aim of this work is to study α7 as one of the therapeutic targets of CBD in order to determine the mechanism by which the phytocannabinoid exerts its effect on the receptor. Wild-type and mutant α7 receptors were expressed in mammalian cells. To evaluate receptor ionotropic function, high-resolution single channel recordings in cell-attached and inside-out patch configurations were used. Changes in intracellular calcium levels were measured by confocal microscopy. We here reveal that CBD modulates α7 ionotropic and metabotropic functions. CBD leads to a concentration-dependent decrease of α7 single-channel activity with an IC50 of 0.54 ± 0.13 µM. The inhibition of α7 activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 conformational states. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 activation, thus decreasing cell calcium responses. The modulation of α7 is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.
Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Esandi, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Sociedad Franco-Argentina de Inmunología
description Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. The aim of this work is to study α7 as one of the therapeutic targets of CBD in order to determine the mechanism by which the phytocannabinoid exerts its effect on the receptor. Wild-type and mutant α7 receptors were expressed in mammalian cells. To evaluate receptor ionotropic function, high-resolution single channel recordings in cell-attached and inside-out patch configurations were used. Changes in intracellular calcium levels were measured by confocal microscopy. We here reveal that CBD modulates α7 ionotropic and metabotropic functions. CBD leads to a concentration-dependent decrease of α7 single-channel activity with an IC50 of 0.54 ± 0.13 µM. The inhibition of α7 activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 conformational states. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 activation, thus decreasing cell calcium responses. The modulation of α7 is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
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/11336/228263
Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 224-224
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228263
identifier_str_mv Modulation of alpha7 nicotinic acetylcholine receptor by cannabidiol; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología & 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 224-224
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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