Reversal of ethanol-induced intoxication by a novel modulator of Gβγ protein potentiation of the glycine receptor

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dc.contributor.authorSan Martin, Loreto
dc.contributor.authorCerda, Fabian
dc.contributor.authorJin, Chunyang
dc.contributor.authorJimenez, Veronica
dc.contributor.authorYevenes, Gonzalo E.
dc.contributor.authorHernandez, Tania
dc.contributor.authorNova, Daniela
dc.contributor.authorFuentealba, Jorge
dc.contributor.authorAguayo, Luis G.
dc.contributor.authorGuzman, Leonardo
dc.date.accessioned2023-09-26T22:14:50Z
dc.date.available2023-09-26T22:14:50Z
dc.date.issued2016-09
dc.descriptionIndexación: Scopus.es
dc.description.abstractThe acute intoxicating effects of ethanol in the central nervous system result from the modulation of several molecular targets. It is widely accepted that ethanol enhances the activity of the glycine receptor (GlyR), thus enhancing inhibitory neurotransmission, leading to motor effects, sedation, and respiratory depression. We previously reported that small peptides interfered with the binding of Gβγ to the GlyR and consequently inhibited the ethanol-induced potentiation of the receptor. Now, using virtual screening, we identified a subset of small molecules capable of interacting with the binding site of Gβγ. One of these compounds, M554, inhibited the ethanol potentiation of the GlyR in both evoked currents and synaptic transmission in vitro. When this compound was tested in vivo in mice treated with ethanol (1–3.5 g/kg), it was found to induce a faster recovery of motor incoordination in rotarod experiments and a shorter sedative effect in loss of righting reflex assays. This study describes a novel molecule that might be relevant for the design of useful therapeutic compounds in the treatment of acute alcohol intoxication.es
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S0021925820307766?via%3Dihub
dc.identifier.citationJournal of Biological Chemistry. Volume 291, Issue 36, Pages 18791 - 18798. 2 September 2016es
dc.identifier.doi10.1074/jbc.M116.740555
dc.identifier.issn0021-9258
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/53333
dc.language.isoenes
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.es
dc.rights.licenseAtribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAlcoholes
dc.subjectG Proteines
dc.subjectGlycine Receptores
dc.subjectMolecular Pharmacologyes
dc.subjectSmall Moleculees
dc.subjectGβγes
dc.titleReversal of ethanol-induced intoxication by a novel modulator of Gβγ protein potentiation of the glycine receptores
dc.typeArtículoes
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