Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes

Autores
Reiner, Gabriela de Las Nieves; Delgado Marín, Leticia Ester; Olguin Alderete, Nair Temis; Sánchez Redondo, S.; Sánchez, Mariela Eugenia; Rodríguez Farré, Eduard; Suñol, Cristina; Garcia, Daniel Asmed
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [3H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl- influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [3H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.
Fil: Reiner, Gabriela de Las Nieves. 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 Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Delgado Marín, Leticia Ester. 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
Fil: Olguin Alderete, Nair Temis. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Sánchez Redondo, S.. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Sánchez, Mariela Eugenia. 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
Fil: Rodríguez Farré, Eduard. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Suñol, Cristina. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
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
Materia
Carvacrol
Chloride Uptake
Chlorothymol
Eugenol
Gabaa Receptor
Membrane Fluidity
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:11336/76927
Acceder
id CONICETDig_ced880eea54dbae132614732262a32cd
oai_identifier_str oai:ri.conicet.gov.ar:11336/76927
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranesReiner, Gabriela de Las NievesDelgado Marín, Leticia EsterOlguin Alderete, Nair TemisSánchez Redondo, S.Sánchez, Mariela EugeniaRodríguez Farré, EduardSuñol, CristinaGarcia, Daniel AsmedCarvacrolChloride UptakeChlorothymolEugenolGabaa ReceptorMembrane Fluidityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [3H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl- influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [3H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.Fil: Reiner, Gabriela de Las Nieves. 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 Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; EspañaFil: Delgado Marín, Leticia Ester. 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; ArgentinaFil: Olguin Alderete, Nair Temis. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; EspañaFil: Sánchez Redondo, S.. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Sánchez, Mariela Eugenia. 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; ArgentinaFil: Rodríguez Farré, Eduard. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Suñol, Cristina. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaFil: 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; ArgentinaHumana Press2013-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76927Reiner, Gabriela de Las Nieves; Delgado Marín, Leticia Ester; Olguin Alderete, Nair Temis; Sánchez Redondo, S.; Sánchez, Mariela Eugenia; et al.; Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes; Humana Press; Cell Biochemistry and Biophysics; 67; 2; 1-3-2013; 515-5251085-91951559-0283CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12013-013-9537-4info:eu-repo/semantics/altIdentifier/doi/10.1007/s12013-013-9537-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:56Zoai:ri.conicet.gov.ar:11336/76927instacron: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:34982025-09-29 09:32:57.179CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
title Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
spellingShingle Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
Reiner, Gabriela de Las Nieves
Carvacrol
Chloride Uptake
Chlorothymol
Eugenol
Gabaa Receptor
Membrane Fluidity
title_short Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
title_full Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
title_fullStr Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
title_full_unstemmed Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
title_sort Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes
dc.creator.none.fl_str_mv Reiner, Gabriela de Las Nieves
Delgado Marín, Leticia Ester
Olguin Alderete, Nair Temis
Sánchez Redondo, S.
Sánchez, Mariela Eugenia
Rodríguez Farré, Eduard
Suñol, Cristina
Garcia, Daniel Asmed
author Reiner, Gabriela de Las Nieves
author_facet Reiner, Gabriela de Las Nieves
Delgado Marín, Leticia Ester
Olguin Alderete, Nair Temis
Sánchez Redondo, S.
Sánchez, Mariela Eugenia
Rodríguez Farré, Eduard
Suñol, Cristina
Garcia, Daniel Asmed
author_role author
author2 Delgado Marín, Leticia Ester
Olguin Alderete, Nair Temis
Sánchez Redondo, S.
Sánchez, Mariela Eugenia
Rodríguez Farré, Eduard
Suñol, Cristina
Garcia, Daniel Asmed
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Carvacrol
Chloride Uptake
Chlorothymol
Eugenol
Gabaa Receptor
Membrane Fluidity
topic Carvacrol
Chloride Uptake
Chlorothymol
Eugenol
Gabaa Receptor
Membrane Fluidity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [3H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl- influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [3H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.
Fil: Reiner, Gabriela de Las Nieves. 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 Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Delgado Marín, Leticia Ester. 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
Fil: Olguin Alderete, Nair Temis. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Sánchez Redondo, S.. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Sánchez, Mariela Eugenia. 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
Fil: Rodríguez Farré, Eduard. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Suñol, Cristina. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
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
description Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [3H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl- influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [3H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.
publishDate 2013
dc.date.none.fl_str_mv 2013-03-01
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/11336/76927
Reiner, Gabriela de Las Nieves; Delgado Marín, Leticia Ester; Olguin Alderete, Nair Temis; Sánchez Redondo, S.; Sánchez, Mariela Eugenia; et al.; Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes; Humana Press; Cell Biochemistry and Biophysics; 67; 2; 1-3-2013; 515-525
1085-9195
1559-0283
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76927
identifier_str_mv Reiner, Gabriela de Las Nieves; Delgado Marín, Leticia Ester; Olguin Alderete, Nair Temis; Sánchez Redondo, S.; Sánchez, Mariela Eugenia; et al.; Gabaergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes; Humana Press; Cell Biochemistry and Biophysics; 67; 2; 1-3-2013; 515-525
1085-9195
1559-0283
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://link.springer.com/article/10.1007%2Fs12013-013-9537-4
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12013-013-9537-4
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.publisher.none.fl_str_mv Humana Press
publisher.none.fl_str_mv Humana Press
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
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score 13.070432

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