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dc.contributor.author
Arias, Hugo Rubén
dc.contributor.author
Vázquez Gómez, Elizabeth
dc.contributor.author
Hernández Abrego, Andy
dc.contributor.author
Gallino, Sofia Ludmila
dc.contributor.author
Feuerbach, Dominik
dc.contributor.author
Ortells, Marcelo Oscar
dc.contributor.author
Elgoyhen, Ana Belen
dc.contributor.author
García Colunga, Jesús
dc.date.available
2019-07-18T20:22:09Z
dc.date.issued
2018-07
dc.identifier.citation
Arias, Hugo Rubén; Vázquez Gómez, Elizabeth; Hernández Abrego, Andy; Gallino, Sofia Ludmila; Feuerbach, Dominik; et al.; Tricyclic antidepressants inhibit hippocampal α7* and α9α10 nicotinic acetylcholine receptors by different mechanisms; Pergamon-Elsevier Science Ltd; International Journal of Biochemistry and Cellular Biology; 100; 7-2018; 1-10
dc.identifier.issn
1357-2725
dc.identifier.uri
http://hdl.handle.net/11336/79849
dc.description.abstract
The activity of tricyclic antidepressants (TCAs) at α7 and α9α10 nicotinic acetylcholine receptors (AChRs) as well as at hippocampal α7-containing (i.e., α7*) AChRs is determined by using Ca 2+ influx and electrophysiological recordings. To determine the inhibitory mechanisms, additional functional tests and molecular docking experiments are performed. The results established that TCAs (a) inhibit Ca 2+ influx in GH3-α7 cells with the following potency (IC 50 in μM) rank: amitriptyline (2.7 ± 0.3) > doxepin (5.9 ± 1.1) ∼ imipramine (6.6 ± 1.0). Interestingly, imipramine inhibits hippocampal α7* AChRs (42.2 ± 8.5 μM) in a noncompetitive and voltage-dependent manner, whereas it inhibits α9α10 AChRs (0.53 ± 0.05 μM) in a competitive and voltage-independent manner, and (b) inhibit [ 3 H]imipramine binding to resting α7 AChRs with the following affinity rank (IC 50 in μM): imipramine (1.6 ± 0.2) > amitriptyline (2.4 ± 0.3) > doxepin (4.9 ± 0.6), whereas imipramine's affinity was no significantly different to that for the desensitized state. The molecular docking and functional results support the notion that imipramine noncompetitively inhibits α7 AChRs by interacting with two overlapping luminal sites, whereas it competitively inhibits α9α10 AChRs by interacting with the orthosteric sites. Collectively our data indicate that TCAs inhibit α7, α9α10, and hippocampal α7* AChRs at clinically relevant concentrations and by different mechanisms of action.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Electrophysiology
dc.subject
Hippocampal Neurons
dc.subject
Mechanisms of Inhibition
dc.subject
Tricyclic Antidepressants
dc.subject
Α7 And Α9α10 Nicotinic Acetylcholine Receptors
dc.subject.classification
Farmacología y Farmacia
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Tricyclic antidepressants inhibit hippocampal α7* and α9α10 nicotinic acetylcholine receptors by different mechanisms
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-07-17T14:41:59Z
dc.journal.volume
100
dc.journal.pagination
1-10
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. California Northstate University College of Medicine; Estados Unidos
dc.description.fil
Fil: Vázquez Gómez, Elizabeth. Universidad Nacional Autónoma de México; México
dc.description.fil
Fil: Hernández Abrego, Andy. Universidad Nacional Autónoma de México; México
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. Universidad de Buenos Aires. Facultad de Medicina; Argentina
dc.description.fil
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
dc.description.fil
Fil: Ortells, Marcelo Oscar. Universidad de Morón. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
dc.description.fil
Fil: García Colunga, Jesús. Universidad Nacional Autónoma de México; México
dc.journal.title
International Journal of Biochemistry and Cellular Biology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1357272518301006
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/29704625
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.biocel.2018.04.017
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