DeltaF508 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 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.
Sidani
Shafik M
SM
Department of Surgery, Yale University, New Haven, Connecticut 06520, USA.
Kirchhoff
Philipp
P
Socrates
Thenral
T
Stelter
Lars
L
Ferreira
Elisa
E
Caputo
Christina
C
Roberts
Kurt E
KE
Bell
Robert L
RL
Egan
Marie E
ME
Geibel
John P
JP
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
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