cAMP triggers Na absorption by distal airway surface epithelium in cystic fibrosis swine.

A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na channel (ENaC), yielding increased Na reabsorption and airway dehydration. We use a non-invasive self-referencing Na-selective microelectrode technique to measure Na transport across individual folds of distal airway surface epithelium preparations from CFTR (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na, while CFTR tissues absorb small, but potentially important, amounts of Na. In cAMP-stimulated conditions, amiloride inhibits Na absorption in CFTR tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na absorption may contribute to dehydration of CF distal airways.