Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/288381
- author
- Chen, D ; Zhao, CM ; Håkanson, Rolf LU ; Samuelson, LC ; Rehfeld, JF and Friis-Hansen, L
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Gastroenterology
- volume
- 126
- issue
- 2
- pages
- 476 - 487
- publisher
- Elsevier
- 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
- 2016-04-01 12:21:27
- date last changed
- 2022-04-13 17:55:26
@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 = {{Elsevier}},
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}},
doi = {{10.1053/j.gastro.2003.11.012}},
volume = {{126}},
year = {{2004}},
}