DeltaF508 mutation results in impaired gastric acid secretion

J Biol Chem. 2007 Mar 2;282(9):6068-74. doi: 10.1074/jbc.M608427200. Epub 2006 Dec 18.

Abstract

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 DeltaF508-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 DeltaF508-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / analysis
  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Gastric Acid / metabolism*
  • Gastric Mucosa / metabolism
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutation*
  • Potassium Channels / analysis
  • Potassium Channels, Inwardly Rectifying / analysis
  • Receptors, Drug / analysis
  • Stomach
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Cystic Fibrosis Transmembrane Conductance Regulator