ΔF508 Mutation Results in Impaired Gastric Acid Secretion

• Published in: The Journal of biological chemistry Vol. 282; no. 9; pp. 6068 - 6074
• Main Authors: Sidani, Shafik M., Kirchhoff, Philipp, Socrates, Thenral, Stelter, Lars, Ferreira, Elisa, Caputo, Christina, Roberts, Kurt E., Bell, Robert L., Egan, Marie E., Geibel, John P.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 02-03-2007; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M608427200

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 (KATP) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and ΔF508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wild-type mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In ΔF508-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 KATP channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion.