The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
V C M ShangR E Roberts

Abstract

Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the loss of barrier function and an elevated sensitivity to environmental insults. An increased release of the endogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients has been reported. The aim of this study was, therefore, to determine the effects of endocannabinoids on bronchial epithelial cell permeability and to investigate the mechanisms involved. Calu-3 human bronchial epithelial cells were cultured at air-liquid interface to allow development of tight junctions. Changes in Transepithelial Electrical Resistance (TEER), a reflection of epithelial permeability, were measured at various time points post-treatment, and expression of the tight junction proteins, occludin and ZO-1, were determined using Western immunoblotting. Anandamide produced a significant reduction in TEER, which was unaffected by cannabinoid receptor antagonists, but attenuated by URB597, an inhibitor of fatty acid amide hydrolase, and by a combination of cyclooxygenase (COX) and lipoxygenase (LOX) blockade. The anandamide metabolite, arachidonic acid, showed similar TEER decrease that was also prevented in the presence of C...Continue Reading

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Citations

Oct 4, 2016·Frontiers in Pharmacology·Caroline TurcotteNicolas Flamand
Oct 30, 2016·Pharmacology & Therapeutics·Roopesh Singh GangwarFrancesca Levi-Schaffer
Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Turgut Emrah Bozkurt
Jan 11, 2021·Clinical Pharmacology and Therapeutics·Lael M YonkerBryan P Hurley
Mar 16, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Lauren F O'LearyDenis J Dupré
May 1, 2021·International Journal of Molecular Sciences·Estefanía MorenoEnric I Canela

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