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Asthma is a chronic inflammatory disease associated with episodic airway narrowing. Inhaled [[beta].sub.2]-adrenergic receptor ([[beta].sub.2]AR) agonists ([[beta].sub.2]-agonists) promote--with limited efficacy--bronchodilation in asthma. All[beta].sub.2]-agonists are canonical orthosteric ligands that bind the same site as endogenous epinephrine. We recently isolated a [[beta].sub.2]AR-selective positive allosteric modulator (PAM), compound-6 (Cmpd-6), which binds outside of the orthosteric site and modulates orthosteric ligand functions. With the emerging therapeutic potential of G-protein coupled receptor allosteric ligands, we investigated the impact of Cmpd-6 on [[beta].sub.2]AR-mediated bronchoprotection. Consistent with our findings using human [[beta].sub.2]ARs, Cmpd-6 allosterically potentiated [[beta].sub.2]-agonist binding to guinea pig [[beta].sub.2]ARs and downstream signaling of [[beta].sub.2]ARs. In contrast, Cmpd6 had no such effect on murine [[beta].sub.2]ARs, which lack a crucial amino acid in the Cmpd-6 allosteric binding site. Importantly, Cmpd-6 enhanced [[BETA].SUB.2] agonist-mediated bronchoprotection against methacholine- induced bronchoconstriction in guinea pig lung slices, but--in line with the binding studies--not in mice. Moreover, Cmpd-6 robustly potentiated [[beta].sub.2] agonist-mediated bronchoprotection against allergen-induced airway constriction in lung slices obtained from a guinea pig model of allergic asthma. Cmpd-6 similarly enhanced [[beta].sub.2] agonist-mediated bronchoprotection against methacholine-induced bronchoconstriction in human lung slices. Our results highlight the potential of [[beta].sub.2]AR- selective PAMs in the treatment of airway narrowing in asthma and other obstructive respiratory diseases., Introduction Asthma is a chronic airway disease that affects millions of people worldwide and is the most common chronic disease in children (1). Although asthma is an airway inflammatory disease, [...]

Jade Wu, PhD, of Duke University School of Medicine, presented on the impact of sleep-wake disorders on mental health at the 2021 Neuroscience Education Institute Congress. In 'Counting Sheep: Improving [...]

Dr. Johnna Friersons office says a lot about her. There's a poster from the movie Hidden Figures on the wall. A notebook --featuring famous women in STEM on the cover [...]