β-ionone facilitates ex vivo airway smooth muscle relaxation via extraocular Opsin-3 light receptor activation.

Abstract

Recent studies have linked deficiencies in β-carotene ingestion and its metabolites with an increased risk and severity of asthma exacerbations. We demonstrate that β-ionone, a β-carotene metabolite, dose-dependently relaxes upper and lower airways in vitro using wire myography of tracheal rings and phase-contrast microscopy of precision-cut lung slices (PCLSs). We demonstrate that β-ionone-induced relaxation is mediated through extraocular opsin-3 (OPN3) receptor activation via pharmacological competitive inhibition with chromophore 9-cis retinal, and through the decreased relaxation demonstrated in Opn3-null PCLSs. We implicate a mechanistic pathway suggestive of G_ɑs activation that is in agreement with our previous findings. Lastly, we confirmed OPN3 expression in airway smooth muscle cells by immunofluorescence and mRNA expression. Our findings implicate β-ionone as a potential therapeutic agent for conditions characterized by bronchoconstriction, such as asthma and COPD. Moreover, this study underscores the significance of dietary intake, particularly of β-carotene rich foods, in maintaining respiratory health.