Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice.
OBJECTIVE
Three pathways control gastric acid secretion: the gastrin-enterochromaffin-like (ECL) cell axis, the vagus-parietal cell axis, and the cholecystokinin (CCK)-D cell axis. Mice lacking gastrin or both gastrin and CCK were examined to determine the role of the hormones.


METHODS
Acid was measured after pylorus ligation, and biopsies from gastrin knockout (KO), gastrin-CCK double-KO, and wild-type (WT) mice were collected for biochemical, immunocytochemical, and electron-microscopic examination.


RESULTS
The ECL cells were inactive in both groups of mutant mice but the cell number was unaffected. Both parietal cell number and level of H(+)/K(+)-ATPase messenger RNA (mRNA) were reduced in the mutant strains, but gastrin-CCK double-KO mice displayed more active parietal cells and larger acid output than the gastrin KO mice. The acid response to histamine in double-KO mice was unchanged whereas that to gastrin was diminished, but it could be restored by infusion of gastrin. Oxyntic D-cell density was the same in both mutant strains, but the D cells were more active in the gastrin KO than in the double-KO mice. CCK infusion in gastrin-CCK double-KO mice raised the somatostatin mRNA level and inhibited acid secretion to the level seen in gastrin KO mice. Vagotomy and atropine abolished acid secretion in all 3 groups of mice.


CONCLUSIONS
Lack of gastrin impairs the gastrin-ECL axis, whereas lack of gastrin and CCK impairs both hormonal pathways. In the gastrin-CCK double-KO mice, acid secretion is only controlled by cholinergic vagal stimulation, which normalizes the acid output.
Chen
Duan
D
Department of Cancer Research & Molecular Medicine, Norweigian University of Science and Technology, Trondheim, Norway.
Zhao
Chun-Mei
CM
Håkanson
Rolf
R
Samuelson
Linda C
LC
Rehfeld
Jens F
JF
Friis-Hansen
Lennart
L
D000818:Animals; D002766:Cholecystokinin / Q000172:deficiency*; D004759:Enterochromaffin Cells / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000378:metabolism; D019864:Somatostatin-Secreting Cells / Q000378:metabolism; D014628:Vagotomy
D005755:Gastrins; D002766:Cholecystokinin