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The endocannabinoid anandamide is an airway relaxant in health and disease

Chronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in v...

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Autores principales: Simon, Annika, von Einem, Thomas, Seidinger, Alexander, Matthey, Michaela, Bindila, Laura, Wenzel, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672354/
https://www.ncbi.nlm.nih.gov/pubmed/36396957
http://dx.doi.org/10.1038/s41467-022-34327-0
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author Simon, Annika
von Einem, Thomas
Seidinger, Alexander
Matthey, Michaela
Bindila, Laura
Wenzel, Daniela
author_facet Simon, Annika
von Einem, Thomas
Seidinger, Alexander
Matthey, Michaela
Bindila, Laura
Wenzel, Daniela
author_sort Simon, Annika
collection PubMed
description Chronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in vivo. In contrast to 2-arachidonlyglycerol-induced airway relaxation, this is mediated by fatty acid amide hydrolase (FAAH)-dependent metabolites. In particular, we identify mouse and also human epithelial and airway smooth muscle cells as source of AEA-induced prostaglandin E2 production and cAMP as direct mediator of AEA-dependent airway relaxation. Mass spectrometry experiments demonstrate reduced levels of endocannabinoid-like compounds in lungs of ovalbumin-sensitized mice indicating a pathophysiological relevance of endocannabinoid signalling in obstructive airway disease. Importantly, AEA inhalation protects against airway hyper-reactivity after ovalbumin sensitization. Thus, this work highlights the AEA/FAAH axis as a critical regulator of airway tone that could provide therapeutic targets for airway relaxation.
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spelling pubmed-96723542022-11-19 The endocannabinoid anandamide is an airway relaxant in health and disease Simon, Annika von Einem, Thomas Seidinger, Alexander Matthey, Michaela Bindila, Laura Wenzel, Daniela Nat Commun Article Chronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in vivo. In contrast to 2-arachidonlyglycerol-induced airway relaxation, this is mediated by fatty acid amide hydrolase (FAAH)-dependent metabolites. In particular, we identify mouse and also human epithelial and airway smooth muscle cells as source of AEA-induced prostaglandin E2 production and cAMP as direct mediator of AEA-dependent airway relaxation. Mass spectrometry experiments demonstrate reduced levels of endocannabinoid-like compounds in lungs of ovalbumin-sensitized mice indicating a pathophysiological relevance of endocannabinoid signalling in obstructive airway disease. Importantly, AEA inhalation protects against airway hyper-reactivity after ovalbumin sensitization. Thus, this work highlights the AEA/FAAH axis as a critical regulator of airway tone that could provide therapeutic targets for airway relaxation. Nature Publishing Group UK 2022-11-17 /pmc/articles/PMC9672354/ /pubmed/36396957 http://dx.doi.org/10.1038/s41467-022-34327-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Simon, Annika
von Einem, Thomas
Seidinger, Alexander
Matthey, Michaela
Bindila, Laura
Wenzel, Daniela
The endocannabinoid anandamide is an airway relaxant in health and disease
title The endocannabinoid anandamide is an airway relaxant in health and disease
title_full The endocannabinoid anandamide is an airway relaxant in health and disease
title_fullStr The endocannabinoid anandamide is an airway relaxant in health and disease
title_full_unstemmed The endocannabinoid anandamide is an airway relaxant in health and disease
title_short The endocannabinoid anandamide is an airway relaxant in health and disease
title_sort endocannabinoid anandamide is an airway relaxant in health and disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672354/
https://www.ncbi.nlm.nih.gov/pubmed/36396957
http://dx.doi.org/10.1038/s41467-022-34327-0
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