ΔF508 mutation results in impaired gastric acid secretion

The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a multifunctional Protein that is involved in Cl- secretion, as well as acting as a regulatory protein. In order for acid secretion to take place a complex interaction of transport proteins and channels must occur at the apical pole of the parietal cell. Included in this process is at least one K+ and Cl- channel, allowing for both recycling of K+ for the H,K-ATPase, and Cl- secretion, necessary for the generation of concentrated HCl in the gastric gland lumen. We have previously shown that an ATP-sensitive potassium channel (K-ATP) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and Delta F508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wildtype mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In Delta F508-deficient mice, however, histamine-induced acid secretion was significantly less than in wild-type mice. Furthermore, immunofluorescent localization of sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the parietal cell, thus further implicating CFTR as the ATP-binding cassette transporter associated with the K-ATP channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion.