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

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Abstract: 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...

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Autores principales: Perillo, Vanesa L., Fernández-Nievas, Gaspar A., Vallés, Ana Sofía, Barrantes, Francisco José, Antollini, Silvia S.
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier B.V. 2019
Materias:
RECEPTORES
PROTEINAS
LIPIDOS
COLESTEROL
ESPECTROSCOPIA
ELECTROFISIOLOGIA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8767
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-8767
record_format dspace
spelling I33-R139-123456789-87672025-04-01T12:15:16Z The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor Perillo, Vanesa L. Fernández-Nievas, Gaspar A. Vallés, Ana Sofía Barrantes, Francisco José Antollini, Silvia S. RECEPTORES PROTEINAS LIPIDOS COLESTEROL ESPECTROSCOPIA ELECTROFISIOLOGIA Abstract: 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 restricted 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 position and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR blockage, 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. 2019-09-19T13:20:45Z 2019-09-19T13:20:45Z 2012 Artículo Perillo VL, Fernández-Nievas GA, Vallés AS, Barrantes FJ, Antollini SS. The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor. Biochimica et Biophysica Acta. 2012; 1818. https://doi.org/10.1016/j.bbamem.2012.06.001. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8767 0006-3002 https://repositorio.uca.edu.ar/handle/123456789/8767 10.1016/j.bbamem.2012.06.001 22699039 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier B.V. Biochimica et Biophysica Acta Vol. 1818, N° 11, 2012
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic RECEPTORES
PROTEINAS
LIPIDOS
COLESTEROL
ESPECTROSCOPIA
ELECTROFISIOLOGIA
spellingShingle RECEPTORES
PROTEINAS
LIPIDOS
COLESTEROL
ESPECTROSCOPIA
ELECTROFISIOLOGIA
Perillo, Vanesa L.
Fernández-Nievas, Gaspar A.
Vallés, Ana Sofía
Barrantes, Francisco José
Antollini, Silvia S.
The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
topic_facet RECEPTORES
PROTEINAS
LIPIDOS
COLESTEROL
ESPECTROSCOPIA
ELECTROFISIOLOGIA
description Abstract: 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 restricted 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 position and isomerism of the torsion angle of unsaturated FFAs are probably a key factor in terms of AChR blockage, 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.
format Artículo
author Perillo, Vanesa L.
Fernández-Nievas, Gaspar A.
Vallés, Ana Sofía
Barrantes, Francisco José
Antollini, Silvia S.
author_facet Perillo, Vanesa L.
Fernández-Nievas, Gaspar A.
Vallés, Ana Sofía
Barrantes, Francisco José
Antollini, Silvia S.
author_sort Perillo, Vanesa L.
title The position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
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 position of the double bond in monounsaturated free fatty acids is essential for the inhibition of the nicotinic acetylcholine receptor
publisher Elsevier B.V.
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8767
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