Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice

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title = "Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice",
abstract = "Background & Aims: 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.",
author = "D Chen and CM Zhao and Rolf H{\aa}kanson and LC Samuelson and JF Rehfeld and L Friis-Hansen",
year = "2004",
doi = "10.1053/j.gastro.2003.11.012",
language = "English",
volume = "126",
pages = "476--487",
journal = "Gastroenterology",
issn = "1528-0012",
publisher = "Elsevier",
number = "2",