Current issues with β2-adrenoceptor agonists: Pharmacology and molecular and cellular mechanisms

Abstract

β2-Adrenoceptors are widely, almost ubiquitously, expressed. Activation of these receptors on bronchial smooth muscle by short- and long-acting β2-adrenoceptor agonists causes bronchodilation. Here, the β2-adrenoceptor is linked by the G protein, Gs, to adenylyl cyclase, which increases cyclic adenosine monophosphate (cAMP), thus activating protein kinase A, which affects calcium levels and reduces the efficiency of myosin light-chain kinase, causing relaxation. Activation also entrains numerous acute and longer term downregulation responses affecting the number, location, and net efficiency of signaling of the receptor. Synthetic β2-agonists are all "partial agonists," incompletely able to ..