Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons

Autores
Garcia, Daniel Asmed; Bujons, Jordi; Vale, Carmen; Suñol, Cristina
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thymol is a naturally occurring phenolic monoterpene known for its anti-microbial and anti-oxidant properties. It is used in dental practice and in anaesthetic halothane preparations. Recent studies have reported enhanced GABAA receptor-operated chloride channel activity and increased binding affinity of [3H]flunitrazepam in the presence of thymol. In the present work, we more closely examined the pharmacological action of thymol on the native GABAA receptor by using primary cultures of cortical neurons. Thymol enhanced GABA-induced (5 μM) chloride influx at concentrations lower than those exhibiting direct activity in the absence of GABA (EC50 = 12 μM and 135 μM, respectively). This direct effect was inhibited by competitive and non-competitive GABAA receptor antagonists. Thymol increased [3H]flunitrazepam binding (EC50 = 131 μM) and showed a tendency to increase [ 3H]muscimol binding. These results confirm that thymol is a positive allosteric modulator of the GABAA receptor. The thymol structural analogues menthol and cymene, which lack an aromatic ring or a hydroxyl group, did not affect [3H]flunitrazepam binding. Using a pharmacophoric model that includes a hydrogen bond donor group as well as an aromatic ring with two aliphatic substituents, we propose to demonstrate the molecular essential features of these compounds to interact with GABAA receptors. Thymol (0-1 mM) did not affect cellular viability.
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España
Fil: Bujons, Jordi. Consejo Superior de Investigaciones Científica; España. Institut d'Investigacions Químiques i Ambientals de Barcelona; España
Fil: Vale, Carmen. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España. Universidad de Santiago de Compostela; España
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España
Materia
Cell Viability
Cultured Cortical Neurons
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
Thymol
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:11336/57589
Acceder
id CONICETDig_084d161af0f232e42a0fe5747ecf14fa
oai_identifier_str oai:ri.conicet.gov.ar:11336/57589
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neuronsGarcia, Daniel AsmedBujons, JordiVale, CarmenSuñol, CristinaCell ViabilityCultured Cortical NeuronsGabaa ReceptorPharmacophore ModelReceptor Binding And Chloride FluxThymolhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Thymol is a naturally occurring phenolic monoterpene known for its anti-microbial and anti-oxidant properties. It is used in dental practice and in anaesthetic halothane preparations. Recent studies have reported enhanced GABAA receptor-operated chloride channel activity and increased binding affinity of [3H]flunitrazepam in the presence of thymol. In the present work, we more closely examined the pharmacological action of thymol on the native GABAA receptor by using primary cultures of cortical neurons. Thymol enhanced GABA-induced (5 μM) chloride influx at concentrations lower than those exhibiting direct activity in the absence of GABA (EC50 = 12 μM and 135 μM, respectively). This direct effect was inhibited by competitive and non-competitive GABAA receptor antagonists. Thymol increased [3H]flunitrazepam binding (EC50 = 131 μM) and showed a tendency to increase [ 3H]muscimol binding. These results confirm that thymol is a positive allosteric modulator of the GABAA receptor. The thymol structural analogues menthol and cymene, which lack an aromatic ring or a hydroxyl group, did not affect [3H]flunitrazepam binding. Using a pharmacophoric model that includes a hydrogen bond donor group as well as an aromatic ring with two aliphatic substituents, we propose to demonstrate the molecular essential features of these compounds to interact with GABAA receptors. Thymol (0-1 mM) did not affect cellular viability.Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; EspañaFil: Bujons, Jordi. Consejo Superior de Investigaciones Científica; España. Institut d'Investigacions Químiques i Ambientals de Barcelona; EspañaFil: Vale, Carmen. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España. Universidad de Santiago de Compostela; EspañaFil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; EspañaPergamon-Elsevier Science Ltd2006-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57589Garcia, Daniel Asmed; Bujons, Jordi; Vale, Carmen; Suñol, Cristina; Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 50; 1; 1-2006; 25-350028-3908CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0028390805002716info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2005.07.009info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:46:22Zoai:ri.conicet.gov.ar:11336/57589instacron: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:34982025-10-15 15:46:23.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
title Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
spellingShingle Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
Garcia, Daniel Asmed
Cell Viability
Cultured Cortical Neurons
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
Thymol
title_short Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
title_full Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
title_fullStr Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
title_full_unstemmed Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
title_sort Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons
dc.creator.none.fl_str_mv Garcia, Daniel Asmed
Bujons, Jordi
Vale, Carmen
Suñol, Cristina
author Garcia, Daniel Asmed
author_facet Garcia, Daniel Asmed
Bujons, Jordi
Vale, Carmen
Suñol, Cristina
author_role author
author2 Bujons, Jordi
Vale, Carmen
Suñol, Cristina
author2_role author
author
author
dc.subject.none.fl_str_mv Cell Viability
Cultured Cortical Neurons
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
Thymol
topic Cell Viability
Cultured Cortical Neurons
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
Thymol
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Thymol is a naturally occurring phenolic monoterpene known for its anti-microbial and anti-oxidant properties. It is used in dental practice and in anaesthetic halothane preparations. Recent studies have reported enhanced GABAA receptor-operated chloride channel activity and increased binding affinity of [3H]flunitrazepam in the presence of thymol. In the present work, we more closely examined the pharmacological action of thymol on the native GABAA receptor by using primary cultures of cortical neurons. Thymol enhanced GABA-induced (5 μM) chloride influx at concentrations lower than those exhibiting direct activity in the absence of GABA (EC50 = 12 μM and 135 μM, respectively). This direct effect was inhibited by competitive and non-competitive GABAA receptor antagonists. Thymol increased [3H]flunitrazepam binding (EC50 = 131 μM) and showed a tendency to increase [ 3H]muscimol binding. These results confirm that thymol is a positive allosteric modulator of the GABAA receptor. The thymol structural analogues menthol and cymene, which lack an aromatic ring or a hydroxyl group, did not affect [3H]flunitrazepam binding. Using a pharmacophoric model that includes a hydrogen bond donor group as well as an aromatic ring with two aliphatic substituents, we propose to demonstrate the molecular essential features of these compounds to interact with GABAA receptors. Thymol (0-1 mM) did not affect cellular viability.
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España
Fil: Bujons, Jordi. Consejo Superior de Investigaciones Científica; España. Institut d'Investigacions Químiques i Ambientals de Barcelona; España
Fil: Vale, Carmen. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España. Universidad de Santiago de Compostela; España
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona; España
description Thymol is a naturally occurring phenolic monoterpene known for its anti-microbial and anti-oxidant properties. It is used in dental practice and in anaesthetic halothane preparations. Recent studies have reported enhanced GABAA receptor-operated chloride channel activity and increased binding affinity of [3H]flunitrazepam in the presence of thymol. In the present work, we more closely examined the pharmacological action of thymol on the native GABAA receptor by using primary cultures of cortical neurons. Thymol enhanced GABA-induced (5 μM) chloride influx at concentrations lower than those exhibiting direct activity in the absence of GABA (EC50 = 12 μM and 135 μM, respectively). This direct effect was inhibited by competitive and non-competitive GABAA receptor antagonists. Thymol increased [3H]flunitrazepam binding (EC50 = 131 μM) and showed a tendency to increase [ 3H]muscimol binding. These results confirm that thymol is a positive allosteric modulator of the GABAA receptor. The thymol structural analogues menthol and cymene, which lack an aromatic ring or a hydroxyl group, did not affect [3H]flunitrazepam binding. Using a pharmacophoric model that includes a hydrogen bond donor group as well as an aromatic ring with two aliphatic substituents, we propose to demonstrate the molecular essential features of these compounds to interact with GABAA receptors. Thymol (0-1 mM) did not affect cellular viability.
publishDate 2006
dc.date.none.fl_str_mv 2006-01
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/11336/57589
Garcia, Daniel Asmed; Bujons, Jordi; Vale, Carmen; Suñol, Cristina; Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 50; 1; 1-2006; 25-35
0028-3908
CONICET Digital
CONICET
url http://hdl.handle.net/11336/57589
identifier_str_mv Garcia, Daniel Asmed; Bujons, Jordi; Vale, Carmen; Suñol, Cristina; Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 50; 1; 1-2006; 25-35
0028-3908
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://www.sciencedirect.com/science/article/pii/S0028390805002716
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2005.07.009
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
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083561007874048
score 13.22299

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