β₂ adrenoceptor signaling regulates ion transport in 16HBE14o- human airway epithelial cells

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 β₂ adrenoceptor subtype, stimulated a similar increase in I_SC , which was inhibited by the β₂ 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 Ca²⁺ levels in 16HBE14o- epithelia confirmed that the I_SC induced by isoprenaline or procaterol involved both cAMP and Ca²⁺ signaling. Our results demonstrate that β₂ adrenoceptors regulate Cl^- secretion in the human airway epithelium by activating apical CFTRs and CaCCs via cAMP-dependent and intracellular Ca²⁺ -dependent mechanisms, respectively.