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In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620702/ https://www.ncbi.nlm.nih.gov/pubmed/37928160 http://dx.doi.org/10.3389/fneur.2023.1270092 |
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author | Mom, Robin Réty, Stéphane Mocquet, Vincent Auguin, Daniel |
author_facet | Mom, Robin Réty, Stéphane Mocquet, Vincent Auguin, Daniel |
author_sort | Mom, Robin |
collection | PubMed |
description | Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However, we recently described for the first time a direct interaction of two corticosteroids (dexamethasone and cortisol) with human AQP2 which strongly inhibited water fluxes. From these initial studies, we proposed an AQPs Corticosteroids Binding Site (ACBS). In the present work, we tested the interaction of 10 molecules associated to the steroid family for this putative ACBS. We observed a wide diversity of affinity and inhibitory potential of these molecules toward AQP2 and discussed the implications for inner ear physiology. Among the tested compounds, cholecalciferol, calcitriol and oestradiol were the most efficient AQP2 water permeability inhibitors. |
format | Online Article Text |
id | pubmed-10620702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106207022023-11-03 In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments Mom, Robin Réty, Stéphane Mocquet, Vincent Auguin, Daniel Front Neurol Neurology Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However, we recently described for the first time a direct interaction of two corticosteroids (dexamethasone and cortisol) with human AQP2 which strongly inhibited water fluxes. From these initial studies, we proposed an AQPs Corticosteroids Binding Site (ACBS). In the present work, we tested the interaction of 10 molecules associated to the steroid family for this putative ACBS. We observed a wide diversity of affinity and inhibitory potential of these molecules toward AQP2 and discussed the implications for inner ear physiology. Among the tested compounds, cholecalciferol, calcitriol and oestradiol were the most efficient AQP2 water permeability inhibitors. Frontiers Media S.A. 2023-10-19 /pmc/articles/PMC10620702/ /pubmed/37928160 http://dx.doi.org/10.3389/fneur.2023.1270092 Text en Copyright © 2023 Mom, Réty, Mocquet and Auguin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Mom, Robin Réty, Stéphane Mocquet, Vincent Auguin, Daniel In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title | In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title_full | In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title_fullStr | In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title_full_unstemmed | In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title_short | In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments |
title_sort | in silico pharmacological study of aqp2 inhibition by steroids contextualized to ménière’s disease treatments |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620702/ https://www.ncbi.nlm.nih.gov/pubmed/37928160 http://dx.doi.org/10.3389/fneur.2023.1270092 |
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