The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor

Autores
Perillo, Vanesa Liliana; Fernández Nievas, Gaspar Antonio; Valles, Ana Sofia; Barrantes, Francisco Jose; Antollini, Silvia Susana
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Free fatty acids (FFAs) are non-competitive antagonists of the nicotinic acetylcholine receptor (AChR). Their site of action is supposedly located at the lipid-AChR interface. To elucidate the mechanism involved in this antagonism, we studied the effect that FFAs with a single double-bond at different positions (ω6, ω9, ω11 and ω13 cis-18:1) have on different AChR properties. Electrophysiological studies showed that only two FFAs (ω6 and ω9) reduced the duration of the channel open-state. The briefest component of the closed- time distribution remained unaltered, suggesting that ω6 and ω9 behave as allosteric blockers. Fluorescence resonance energy transfer studies indicated that all FFAs locate at the lipid-AChR interface, ω6 being restrict- ed to annular sites and all others occupying non-annular sites. The perturbation of the native membrane order by FFAs was evaluated by DPH (1,6-diphenyl-1,3,5-hexatriene) and Laurdan fluorescence polarization studies, with the greatest decrease observed for ω9 and ω11. AChR conformational changes produced by FFAs present at the lipid bilayer were evaluated by fluorescence quenching studies of pyrene-labeled AChR and also using the AChR conformational-sensitive probe crystal violet. All cis-FFAs produced AChR conformational changes at the transmembrane level, but only ω9, ω11 and ω13 perturbed the resting state. Thus, the posi- tion and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR block- age, suggesting that FFAs with a unique cis double bond at a superficial position inside the membrane directly inhibit AChR function by perturbing a potential conserved core structure for AChR gating at that level.
Fil: Perillo, Vanesa Liliana. 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
Fil: Fernández Nievas, Gaspar Antonio. 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
Fil: Valles, Ana Sofia. 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
Fil: Barrantes, Francisco Jose. 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. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Antollini, Silvia Susana. 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
Materia
Nicotinic acetylcholine receptor
Lipid–protein interaction
Free fatty acid
Fluorescence spectroscopy
Electrophysiology
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:11336/257738
Acceder
id CONICETDig_f91474284451fe57130e5e08f0ddf439
oai_identifier_str oai:ri.conicet.gov.ar:11336/257738
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptorPerillo, Vanesa LilianaFernández Nievas, Gaspar AntonioValles, Ana SofiaBarrantes, Francisco JoseAntollini, Silvia SusanaNicotinic acetylcholine receptorLipid–protein interactionFree fatty acidFluorescence spectroscopyElectrophysiologyhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Free fatty acids (FFAs) are non-competitive antagonists of the nicotinic acetylcholine receptor (AChR). Their site of action is supposedly located at the lipid-AChR interface. To elucidate the mechanism involved in this antagonism, we studied the effect that FFAs with a single double-bond at different positions (ω6, ω9, ω11 and ω13 cis-18:1) have on different AChR properties. Electrophysiological studies showed that only two FFAs (ω6 and ω9) reduced the duration of the channel open-state. The briefest component of the closed- time distribution remained unaltered, suggesting that ω6 and ω9 behave as allosteric blockers. Fluorescence resonance energy transfer studies indicated that all FFAs locate at the lipid-AChR interface, ω6 being restrict- ed to annular sites and all others occupying non-annular sites. The perturbation of the native membrane order by FFAs was evaluated by DPH (1,6-diphenyl-1,3,5-hexatriene) and Laurdan fluorescence polarization studies, with the greatest decrease observed for ω9 and ω11. AChR conformational changes produced by FFAs present at the lipid bilayer were evaluated by fluorescence quenching studies of pyrene-labeled AChR and also using the AChR conformational-sensitive probe crystal violet. All cis-FFAs produced AChR conformational changes at the transmembrane level, but only ω9, ω11 and ω13 perturbed the resting state. Thus, the posi- tion and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR block- age, suggesting that FFAs with a unique cis double bond at a superficial position inside the membrane directly inhibit AChR function by perturbing a potential conserved core structure for AChR gating at that level.Fil: Perillo, Vanesa Liliana. 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; ArgentinaFil: Fernández Nievas, Gaspar Antonio. 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; ArgentinaFil: Valles, Ana Sofia. 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; ArgentinaFil: Barrantes, Francisco Jose. 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. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Antollini, Silvia Susana. 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; ArgentinaElsevier Science2012-06-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/257738Perillo, Vanesa Liliana; Fernández Nievas, Gaspar Antonio; Valles, Ana Sofia; Barrantes, Francisco Jose; Antollini, Silvia Susana; The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1818; 11; 12-6-2012; 2511-25200005-27361879-2642CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0005273612001897?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2012.06.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:29:41Zoai:ri.conicet.gov.ar:11336/257738instacron: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 11:29:41.9CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
title The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
spellingShingle The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
Perillo, Vanesa Liliana
Nicotinic acetylcholine receptor
Lipid–protein interaction
Free fatty acid
Fluorescence spectroscopy
Electrophysiology
title_short The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
title_full The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
title_fullStr The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
title_full_unstemmed The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
title_sort The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
dc.creator.none.fl_str_mv Perillo, Vanesa Liliana
Fernández Nievas, Gaspar Antonio
Valles, Ana Sofia
Barrantes, Francisco Jose
Antollini, Silvia Susana
author Perillo, Vanesa Liliana
author_facet Perillo, Vanesa Liliana
Fernández Nievas, Gaspar Antonio
Valles, Ana Sofia
Barrantes, Francisco Jose
Antollini, Silvia Susana
author_role author
author2 Fernández Nievas, Gaspar Antonio
Valles, Ana Sofia
Barrantes, Francisco Jose
Antollini, Silvia Susana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Nicotinic acetylcholine receptor
Lipid–protein interaction
Free fatty acid
Fluorescence spectroscopy
Electrophysiology
topic Nicotinic acetylcholine receptor
Lipid–protein interaction
Free fatty acid
Fluorescence spectroscopy
Electrophysiology
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Free fatty acids (FFAs) are non-competitive antagonists of the nicotinic acetylcholine receptor (AChR). Their site of action is supposedly located at the lipid-AChR interface. To elucidate the mechanism involved in this antagonism, we studied the effect that FFAs with a single double-bond at different positions (ω6, ω9, ω11 and ω13 cis-18:1) have on different AChR properties. Electrophysiological studies showed that only two FFAs (ω6 and ω9) reduced the duration of the channel open-state. The briefest component of the closed- time distribution remained unaltered, suggesting that ω6 and ω9 behave as allosteric blockers. Fluorescence resonance energy transfer studies indicated that all FFAs locate at the lipid-AChR interface, ω6 being restrict- ed to annular sites and all others occupying non-annular sites. The perturbation of the native membrane order by FFAs was evaluated by DPH (1,6-diphenyl-1,3,5-hexatriene) and Laurdan fluorescence polarization studies, with the greatest decrease observed for ω9 and ω11. AChR conformational changes produced by FFAs present at the lipid bilayer were evaluated by fluorescence quenching studies of pyrene-labeled AChR and also using the AChR conformational-sensitive probe crystal violet. All cis-FFAs produced AChR conformational changes at the transmembrane level, but only ω9, ω11 and ω13 perturbed the resting state. Thus, the posi- tion and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR block- age, suggesting that FFAs with a unique cis double bond at a superficial position inside the membrane directly inhibit AChR function by perturbing a potential conserved core structure for AChR gating at that level.
Fil: Perillo, Vanesa Liliana. 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
Fil: Fernández Nievas, Gaspar Antonio. 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
Fil: Valles, Ana Sofia. 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
Fil: Barrantes, Francisco Jose. 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. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Antollini, Silvia Susana. 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
description Free fatty acids (FFAs) are non-competitive antagonists of the nicotinic acetylcholine receptor (AChR). Their site of action is supposedly located at the lipid-AChR interface. To elucidate the mechanism involved in this antagonism, we studied the effect that FFAs with a single double-bond at different positions (ω6, ω9, ω11 and ω13 cis-18:1) have on different AChR properties. Electrophysiological studies showed that only two FFAs (ω6 and ω9) reduced the duration of the channel open-state. The briefest component of the closed- time distribution remained unaltered, suggesting that ω6 and ω9 behave as allosteric blockers. Fluorescence resonance energy transfer studies indicated that all FFAs locate at the lipid-AChR interface, ω6 being restrict- ed to annular sites and all others occupying non-annular sites. The perturbation of the native membrane order by FFAs was evaluated by DPH (1,6-diphenyl-1,3,5-hexatriene) and Laurdan fluorescence polarization studies, with the greatest decrease observed for ω9 and ω11. AChR conformational changes produced by FFAs present at the lipid bilayer were evaluated by fluorescence quenching studies of pyrene-labeled AChR and also using the AChR conformational-sensitive probe crystal violet. All cis-FFAs produced AChR conformational changes at the transmembrane level, but only ω9, ω11 and ω13 perturbed the resting state. Thus, the posi- tion and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR block- age, suggesting that FFAs with a unique cis double bond at a superficial position inside the membrane directly inhibit AChR function by perturbing a potential conserved core structure for AChR gating at that level.
publishDate 2012
dc.date.none.fl_str_mv 2012-06-12
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/11336/257738
Perillo, Vanesa Liliana; Fernández Nievas, Gaspar Antonio; Valles, Ana Sofia; Barrantes, Francisco Jose; Antollini, Silvia Susana; The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1818; 11; 12-6-2012; 2511-2520
0005-2736
1879-2642
CONICET Digital
CONICET
url http://hdl.handle.net/11336/257738
identifier_str_mv Perillo, Vanesa Liliana; Fernández Nievas, Gaspar Antonio; Valles, Ana Sofia; Barrantes, Francisco Jose; Antollini, Silvia Susana; The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1818; 11; 12-6-2012; 2511-2520
0005-2736
1879-2642
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/S0005273612001897?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2012.06.001
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.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 12.982451

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