Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides

Autores
Asis Rodriguez, Marcos Alberto; Felsztyna, Iván; Garcia, Daniel Asmed; Sánchez, Mariela Eugenia; Miguel, Virginia
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Fluralaner and Fipronil are gabaergic insecticides belonging to the non-competitive antagonists NCA-I and NCA-II families, respectively. While fipronil binds to the pore of the insect homopentameric GABAA receptor (RDL), fluralaner targets a site located in the transmembrane region, at the receptor subunits interface. There is a major interest in the development of highly selective insecticides that are not toxic to vertebrates. In this context, it is interesting the fact that, unlike mammal membranes, which are mainly composed of phosphatidylcholine (PC) lipids, sphingolipids and sterols; insects cannot synthesize sterols. Therefore, they modulate membrane fluidity through the modification of the PC/phosphatidylethanolamine (PE) lipids ratio. This variation in the composition of the membrane of vertebrates and insects could be relevant when we analyze the nonspecific effects of lipophilic compounds on the structure and dynamics of the membrane and ultimately of RDL. Due to the lipophilicity of these compounds, and the location of the receptor binding site for fluralaner, it is probable that these insecticides could reach their binding site through the lipid bilayer. We performed Free diffusion MD simulations of POPC bilayers with increasing concentrations of Cholesterol (CHOL) or POPE, in the absence and in presence of fluralaner or fipronil. Fluralaner and fipronil acted differentially in membranes with the same composition. The analysis of these trajectories showed that fluralaner has a marked effect on the physical properties of binary bilayers containing POPE, and a negligible effect on bilayers containing CHOL. The opposite is true in the case of fipronil. On the other hand, both, fluralaner and fipronil, reduced the CHOL flip-flop rates, except for the POPC-CHOL 1:1 system in which fipronil enhanced it considerably. Our results suggest that fipronil and fluralaner may impact differentially on the physical properties of both types of membranes.
Fil: Asis Rodriguez, Marcos Alberto. 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: Felsztyna, Iván. 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: 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
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: Miguel, Virginia. 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
L Reunion Anual de la Sociedad Argentina de Biofisica
Rosario
Argentina
Sociedad Argentina de Biofísica
Universidad Nacional de Rosario
Materia
fipronil
fluralaner
insect membranes
mimetic
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:11336/234446
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/234446
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticidesAsis Rodriguez, Marcos AlbertoFelsztyna, IvánGarcia, Daniel AsmedSánchez, Mariela EugeniaMiguel, Virginiafipronilfluralanerinsect membranesmimetichttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fluralaner and Fipronil are gabaergic insecticides belonging to the non-competitive antagonists NCA-I and NCA-II families, respectively. While fipronil binds to the pore of the insect homopentameric GABAA receptor (RDL), fluralaner targets a site located in the transmembrane region, at the receptor subunits interface. There is a major interest in the development of highly selective insecticides that are not toxic to vertebrates. In this context, it is interesting the fact that, unlike mammal membranes, which are mainly composed of phosphatidylcholine (PC) lipids, sphingolipids and sterols; insects cannot synthesize sterols. Therefore, they modulate membrane fluidity through the modification of the PC/phosphatidylethanolamine (PE) lipids ratio. This variation in the composition of the membrane of vertebrates and insects could be relevant when we analyze the nonspecific effects of lipophilic compounds on the structure and dynamics of the membrane and ultimately of RDL. Due to the lipophilicity of these compounds, and the location of the receptor binding site for fluralaner, it is probable that these insecticides could reach their binding site through the lipid bilayer. We performed Free diffusion MD simulations of POPC bilayers with increasing concentrations of Cholesterol (CHOL) or POPE, in the absence and in presence of fluralaner or fipronil. Fluralaner and fipronil acted differentially in membranes with the same composition. The analysis of these trajectories showed that fluralaner has a marked effect on the physical properties of binary bilayers containing POPE, and a negligible effect on bilayers containing CHOL. The opposite is true in the case of fipronil. On the other hand, both, fluralaner and fipronil, reduced the CHOL flip-flop rates, except for the POPC-CHOL 1:1 system in which fipronil enhanced it considerably. Our results suggest that fipronil and fluralaner may impact differentially on the physical properties of both types of membranes.Fil: Asis Rodriguez, Marcos Alberto. 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: Felsztyna, Iván. 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: 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; ArgentinaFil: 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: Miguel, Virginia. 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; ArgentinaL Reunion Anual de la Sociedad Argentina de BiofisicaRosarioArgentinaSociedad Argentina de BiofísicaUniversidad Nacional de RosarioSociedad Argentina de BiofísicaAmbroggio, Ernesto EstebanCelej, Maria SoledadAcierno, Juan Pablo2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/234446Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides; L Reunion Anual de la Sociedad Argentina de Biofisica; Rosario; Argentina; 2022; 108-108978-987-48938-0-2CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:12:20Zoai:ri.conicet.gov.ar:11336/234446instacron: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 11:12:21.071CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
title Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
spellingShingle Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
Asis Rodriguez, Marcos Alberto
fipronil
fluralaner
insect membranes
mimetic
title_short Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
title_full Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
title_fullStr Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
title_full_unstemmed Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
title_sort Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides
dc.creator.none.fl_str_mv Asis Rodriguez, Marcos Alberto
Felsztyna, Iván
Garcia, Daniel Asmed
Sánchez, Mariela Eugenia
Miguel, Virginia
author Asis Rodriguez, Marcos Alberto
author_facet Asis Rodriguez, Marcos Alberto
Felsztyna, Iván
Garcia, Daniel Asmed
Sánchez, Mariela Eugenia
Miguel, Virginia
author_role author
author2 Felsztyna, Iván
Garcia, Daniel Asmed
Sánchez, Mariela Eugenia
Miguel, Virginia
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ambroggio, Ernesto Esteban
Celej, Maria Soledad
Acierno, Juan Pablo
dc.subject.none.fl_str_mv fipronil
fluralaner
insect membranes
mimetic
topic fipronil
fluralaner
insect membranes
mimetic
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Fluralaner and Fipronil are gabaergic insecticides belonging to the non-competitive antagonists NCA-I and NCA-II families, respectively. While fipronil binds to the pore of the insect homopentameric GABAA receptor (RDL), fluralaner targets a site located in the transmembrane region, at the receptor subunits interface. There is a major interest in the development of highly selective insecticides that are not toxic to vertebrates. In this context, it is interesting the fact that, unlike mammal membranes, which are mainly composed of phosphatidylcholine (PC) lipids, sphingolipids and sterols; insects cannot synthesize sterols. Therefore, they modulate membrane fluidity through the modification of the PC/phosphatidylethanolamine (PE) lipids ratio. This variation in the composition of the membrane of vertebrates and insects could be relevant when we analyze the nonspecific effects of lipophilic compounds on the structure and dynamics of the membrane and ultimately of RDL. Due to the lipophilicity of these compounds, and the location of the receptor binding site for fluralaner, it is probable that these insecticides could reach their binding site through the lipid bilayer. We performed Free diffusion MD simulations of POPC bilayers with increasing concentrations of Cholesterol (CHOL) or POPE, in the absence and in presence of fluralaner or fipronil. Fluralaner and fipronil acted differentially in membranes with the same composition. The analysis of these trajectories showed that fluralaner has a marked effect on the physical properties of binary bilayers containing POPE, and a negligible effect on bilayers containing CHOL. The opposite is true in the case of fipronil. On the other hand, both, fluralaner and fipronil, reduced the CHOL flip-flop rates, except for the POPC-CHOL 1:1 system in which fipronil enhanced it considerably. Our results suggest that fipronil and fluralaner may impact differentially on the physical properties of both types of membranes.
Fil: Asis Rodriguez, Marcos Alberto. 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: Felsztyna, Iván. 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: 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
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: Miguel, Virginia. 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
L Reunion Anual de la Sociedad Argentina de Biofisica
Rosario
Argentina
Sociedad Argentina de Biofísica
Universidad Nacional de Rosario
description Fluralaner and Fipronil are gabaergic insecticides belonging to the non-competitive antagonists NCA-I and NCA-II families, respectively. While fipronil binds to the pore of the insect homopentameric GABAA receptor (RDL), fluralaner targets a site located in the transmembrane region, at the receptor subunits interface. There is a major interest in the development of highly selective insecticides that are not toxic to vertebrates. In this context, it is interesting the fact that, unlike mammal membranes, which are mainly composed of phosphatidylcholine (PC) lipids, sphingolipids and sterols; insects cannot synthesize sterols. Therefore, they modulate membrane fluidity through the modification of the PC/phosphatidylethanolamine (PE) lipids ratio. This variation in the composition of the membrane of vertebrates and insects could be relevant when we analyze the nonspecific effects of lipophilic compounds on the structure and dynamics of the membrane and ultimately of RDL. Due to the lipophilicity of these compounds, and the location of the receptor binding site for fluralaner, it is probable that these insecticides could reach their binding site through the lipid bilayer. We performed Free diffusion MD simulations of POPC bilayers with increasing concentrations of Cholesterol (CHOL) or POPE, in the absence and in presence of fluralaner or fipronil. Fluralaner and fipronil acted differentially in membranes with the same composition. The analysis of these trajectories showed that fluralaner has a marked effect on the physical properties of binary bilayers containing POPE, and a negligible effect on bilayers containing CHOL. The opposite is true in the case of fipronil. On the other hand, both, fluralaner and fipronil, reduced the CHOL flip-flop rates, except for the POPC-CHOL 1:1 system in which fipronil enhanced it considerably. Our results suggest that fipronil and fluralaner may impact differentially on the physical properties of both types of membranes.
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
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/11336/234446
Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides; L Reunion Anual de la Sociedad Argentina de Biofisica; Rosario; Argentina; 2022; 108-108
978-987-48938-0-2
CONICET Digital
CONICET
url http://hdl.handle.net/11336/234446
identifier_str_mv Effects of the composition of insects and mammals membranes on the non-specific action of GABAergic insecticides; L Reunion Anual de la Sociedad Argentina de Biofisica; Rosario; Argentina; 2022; 108-108
978-987-48938-0-2
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://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
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
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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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