cAMP stimulation of HCO3- secretion across airway epithelia

To test for the presence of HCO(3)(-) transport across airway epithelia, we measured short-circuit current in primary cultures of canine and human airway epithelia bathed in a Cl(-)-free, HCO(3)(-)/CO(2)-buffered solution. cAMP agonists stimulated a secretory current that was likely carried by HCO(3)(-) because it was absent in HCO(3)(-)-free solutions. In addition, the cAMP-stimulated current was inhibited by the carbonic anhydrase inhibitor, acetazolamide, and by the apical addition of a blocker of cystic fibrosis transmembrane conductance regulator (CFTR), diphenylamine-2-carboxylate. The current was dependent on Na(+) because it was inhibited by removing Na(+) from the submucosal solution and by inhibition of the Na(+)-K(+)-ATPase with ouabain. The cAMP-stimulated current was absent in cystic fibrosis (CF) airway epithelia. These data suggest that cAMP agonists can stimulate HCO(3)(-) secretion across airway epithelia and that CFTR may provide a conductive pathway for HCO(3)(-) movement across the apical membrane.