Mostrar el registro sencillo del ítem
dc.contributor.author
Arias, Hugo Rubén
dc.contributor.author
Jin, Xiao Tao
dc.contributor.author
Gallino, Sofia Ludmila
dc.contributor.author
Peng, Can
dc.contributor.author
Feuerbach, Dominik
dc.contributor.author
García Colunga, Jesús
dc.contributor.author
Elgoyhen, Ana Belen
dc.contributor.author
Drenan, Ryan M.
dc.contributor.author
Ortells, Marcelo Oscar
dc.date.available
2020-12-17T20:07:07Z
dc.date.issued
2019-12
dc.identifier.citation
Arias, Hugo Rubén; Jin, Xiao Tao; Gallino, Sofia Ludmila; Peng, Can; Feuerbach, Dominik; et al.; Selectivity of (±)-citalopram at nicotinic acetylcholine receptors and different inhibitory mechanisms between habenular α3β4* and α9α10 subtypes; Pergamon-Elsevier Science Ltd; Neurochemistry International; 131; 104552; 12-2019; 1-14
dc.identifier.issn
0197-0186
dc.identifier.uri
http://hdl.handle.net/11336/120790
dc.description.abstract
The inhibitory activity of (±)-citalopram on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors(AChRs) was determined by Ca2+ influx assays, whereas its effect on rat α9α10 and mouse habenular α3β4*AChRs by electrophysiological recordings. The Ca2+ influx results clearly establish that (±)-citalopram inhibits(IC50´s in μM) hα3β4 AChRs (5.1 ± 1.3) with higher potency than that for hα7 (18.8 ± 1.1) and hα4β2(19.1 ± 4.2) AChRs. This is in agreement with the [3H]imipramine competition binding results indicating that(±)-citalopram binds to imipramine sites at desensitized hα3β4 with>2-fold higher affinity than that forhα4β2. The electrophysiological, molecular docking, and in silico mutation results indicate that (±)-citalopramcompetitively inhibits rα9α10 AChRs (7.5 ± 0.9) in a voltage-independent manner by interacting mainly withorthosteric sites, whereas it inhibits a homogeneous population of α3β4* AChRs at MHb (VI) neurons(7.6 ± 1.0) in a voltage-dependent manner by interacting mainly with a luminal site located in the middle ofthe ion channel, overlapping the imipramine site, which suggests an ion channel blocking mechanism. In conclusion,(±)-citalopram inhibits α3β4 and α9α10 AChRs with higher potency compared to other AChRs but bydifferent mechanisms. (±)-Citalopram also inhibits habenular α3β4*AChRs, supporting the notion that thesereceptors are important endogenous targets related to their anti-addictive activities.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
(±)-CITALOPRAM
dc.subject
BRAIN SLICES
dc.subject
MEDIAL HABENULA
dc.subject
NICOTINIC ACETYLCHOLINE RECEPTOR
dc.subject
SELECTIVE SEROTONIN REUPTAKE INHIBITOR
dc.subject.classification
Farmacología y Farmacia
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Selectivity of (±)-citalopram at nicotinic acetylcholine receptors and different inhibitory mechanisms between habenular α3β4* and α9α10 subtypes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-18T21:17:32Z
dc.journal.volume
131
dc.journal.number
104552
dc.journal.pagination
1-14
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Arias, Hugo Rubén. Oklahoma State University; Estados Unidos
dc.description.fil
Fil: Jin, Xiao Tao. Northwestern University; Estados Unidos
dc.description.fil
Fil: Gallino, Sofia Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Peng, Can. Northwestern University; Estados Unidos
dc.description.fil
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
dc.description.fil
Fil: García Colunga, Jesús. Universidad Nacional Autónoma de México; México
dc.description.fil
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina
dc.description.fil
Fil: Drenan, Ryan M.. Northwestern University; Estados Unidos
dc.description.fil
Fil: Ortells, Marcelo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Morón; Argentina
dc.journal.title
Neurochemistry International
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0197018619303651
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neuint.2019.104552
Archivos asociados