The endocannabinoid anandamide is an airway relaxant in health and disease

Annika Simon, Thomas Einem, Alexander Seidinger, Michaela Matthey, Laura Bindila and Daniela Wenzel ()
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Annika Simon: Ruhr University of Bochum
Thomas Einem: University of Bonn
Alexander Seidinger: Ruhr University of Bochum
Michaela Matthey: Ruhr University of Bochum
Laura Bindila: University Medical Center of the Johannes Gutenberg University of Mainz
Daniela Wenzel: Ruhr University of Bochum

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34327-0

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