title: DeltaF508 mutation results in impaired gastric acid secretion.
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.
authors.affiliation: Department of Surgery, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Shafik M
authors.initials: SM
authors.lastname: Sidani
authors.forename: Philipp
authors.initials: P
authors.lastname: Kirchhoff
authors.forename: Thenral
authors.initials: T
authors.lastname: Socrates
authors.forename: Lars
authors.initials: L
authors.lastname: Stelter
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferreira
authors.forename: Christina
authors.initials: C
authors.lastname: Caputo
authors.forename: Kurt E
authors.initials: KE
authors.lastname: Roberts
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bell
authors.forename: Marie E
authors.initials: ME
authors.lastname: Egan
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D015221:Potassium Channels / Q000032:analysis; D024661:Potassium Channels, Inwardly Rectifying / Q000032:analysis; D011955:Receptors, Drug / Q000032:analysis; D013270:Stomach; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator