ß2 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 ß adrenoceptor agonist isoprenaline stimulated an increase in short-circuit current (ISC ), which was inhibited by the ß adrenoceptor blocker propranolol. Treatment with procaterol, an agonist specific for the ß2 adrenoceptor subtype, stimulated a similar increase in ISC , which was inhibited by the ß2 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 ISC . "Trimultaneous" recording of ISC and intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ levels in 16HBE14o- epithelia confirmed that the ISC induced by isoprenaline or procaterol involved both cAMP and Ca2+ signaling. Our results demonstrate that ß2 adrenoceptors regulate Cl- secretion in the human airway epithelium by activating apical CFTRs and CaCCs via cAMP-dependent and intracellular Ca2+ -dependent mechanisms, respectively.