Cytokines regulate beta-2-adrenergic receptor responsiveness in airway smooth muscle via multiple PKA- and EP2 receptor-dependent mechanisms.

Beta2AR desensitization in airway smooth muscle (ASM) mediated by airway inflammation has been proposed to contribute to asthma pathogenesis and diminished efficacy of beta-agonist therapy. Mechanistic insight into this phenomenon is largely conceptual and lacks direct empirical evidence. Here, we employ molecular and genetic strategies to reveal mechanisms mediating cytokine effects on ASM beta2AR responsiveness.

Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models.

We determined the relative rank orders of anticholinergic potencies of 10 antihistamines in two functional bioassays: (1) an in vitro assay measuring inhibition of carbachol-induced contractions of isolated guinea pig trachealis muscle, (2) an in vivo bioassay comparing systemic hypotensive responses to bolus i.v. injections of acetylcholine before and after infusions of an antihistamine in anaesthetized rats.