Inhaled β₂-adrenoceptor (β₂-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β₂-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β₂-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β₂-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised.
Keywords: G-protein-coupled receptor signaling; airway smooth muscle; bronchodilation; desensitization; safety issues; β2-adrenoceptors.