Different classes of antidepressants inhibit the rat α7 nicotinic acetylcholine receptor by interacting within the ion channel: A functional and structural study

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dc.contributor.authorDuarte, Yorley
dc.contributor.authorRojas, Maximiliano
dc.contributor.authorCanan, Jonathan
dc.contributor.authorPérez, Edwin G.
dc.contributor.authorGonzález-Nilo, Fernando
dc.contributor.authorGarcía-Colunga, Jesús
dc.date.accessioned2023-03-31T14:43:57Z
dc.date.available2023-03-31T14:43:57Z
dc.date.issued2021-02
dc.descriptionIndexación: Scopuses
dc.description.abstractSeveral antidepressants inhibit nicotinic acetylcholine receptors (nAChRs) in a noncompetitive and voltage-dependent fashion. Here, we asked whether antidepressants with a different structure and pharmacological pro le modulate the rat α7 nAChR through a similar mechanism by interacting within the ion-channel. We applied electrophysiological (recording of the ion current elicited by choline, ICh, which activates α7 nAChRs from rat CA1 hippocampal interneurons) and in silico approaches (homology modeling of the rat α7 nAChR, molecular docking, molecular dynamics simulations, and binding free energy calculations). The antidepressants inhibited IChwith the order: Norfluoxetine ~ mirtazapine ~ imipramine < bupropion ~ fluoxetine ~ venlafaxine ~ escitalopram. The constructed homology model of the rat α7 nAChR resulted in the extracellular vestibule and the channel pore is highly negatively charged, which facilitates the permeation of cations and the entrance of the protonated form of antidepressants. Molecular docking and molecular dynamics simulations were carried out within the ion-channel of the α7 nAChR, revealing that the antidepressants adopt poses along the receptor channel, with slightly different binding-free energy values. Furthermore, the inhibition of ICh and free energy values for each antidepressant-receptor complex were highly correlated. Thus, the α7 nAChR is negatively modulated by a variety of antidepressants interacting in the ion-channel. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.es
dc.description.urihttps://www.mdpi.com/1420-3049/26/4/998
dc.identifier.citationMolecules Volume 26, Issue 42 February 2021 Article number 998es
dc.identifier.doi10.3390/molecules26040998
dc.identifier.issn1420-3049
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/48091
dc.language.isoenes
dc.publisherMDPIes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAllosteric modulatorses
dc.subjectAntidepressantses
dc.subjectBiological activityes
dc.subjectHippocampuses
dc.subjectIn silico studieses
dc.subjectα7 nicotinic acetylcholine receptorses
dc.titleDifferent classes of antidepressants inhibit the rat α7 nicotinic acetylcholine receptor by interacting within the ion channel: A functional and structural studyes
dc.typeArtículoes
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