β 2 adrenoceptor signaling regulates ion transport in 16HBE14o‐ human airway epithelial cells

Abstract We investigated the regulation of Cl − secretion by adrenoceptors in polarized 16HBE14o‐ human bronchial epithelial cells. Treatment with the nonselective β adrenoceptor agonist isoprenaline stimulated an increase in short‐circuit current ( I SC ), which was inhibited by the β adrenoceptor blocker propranolol. Treatment with procaterol, an agonist specific for the β 2 adrenoceptor subtype, stimulated a similar increase in I SC , which was inhibited by the β 2 adrenoceptor antagonist ICI 118551. Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium‐activated Cl − channel (CaCC), but not K + channel blockers, were able to inhibit the increase in I SC . “Trimultaneous” recording of I SC and intracellular cyclic adenosine monophosphate (cAMP) and Ca 2+ levels in 16HBE14o‐ epithelia confirmed that the I SC induced by isoprenaline or procaterol involved both cAMP and Ca 2+ signaling. Our results demonstrate that β 2 adrenoceptors regulate Cl − secretion in the human airway epithelium by activating apical CFTRs and CaCCs via cAMP‐dependent and intracellular Ca 2+ ‐dependent mechanisms, respectively.