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

Chen, D; Zhao, CM; Håkanson, Rolf LU ; Samuelson, LC; Rehfeld, JF and Friis-Hansen, L (2004) In Gastroenterology 126(2). p.476-487
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Gastroenterology
volume
126
issue
2
pages
476 - 487
publisher
W B Saunders
external identifiers
  • wos:000188811100015
  • pmid:14762785
  • scopus:0842321802
ISSN
1528-0012
DOI
10.1053/j.gastro.2003.11.012
language
English
LU publication?
yes
id
f5e2779a-b97e-48fb-822c-da4723aa1ec7 (old id 288381)
date added to LUP
2007-08-02 11:22:20
date last changed
2017-10-01 03:53:12
@article{f5e2779a-b97e-48fb-822c-da4723aa1ec7,
  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       = {Chen, D and Zhao, CM and Håkanson, Rolf and Samuelson, LC and Rehfeld, JF and Friis-Hansen, L},
  issn         = {1528-0012},
  language     = {eng},
  number       = {2},
  pages        = {476--487},
  publisher    = {W B Saunders},
  series       = {Gastroenterology},
  title        = {Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice},
  url          = {http://dx.doi.org/10.1053/j.gastro.2003.11.012},
  volume       = {126},
  year         = {2004},
}