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Altered control of ...
Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice
- Article/chapterEnglish2004
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LIBRIS-ID:oai:lup.lub.lu.se:f5e2779a-b97e-48fb-822c-da4723aa1ec7
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https://lup.lub.lu.se/record/288381URI
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https://doi.org/10.1053/j.gastro.2003.11.012DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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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.
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Zhao, CM
(author)
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Håkanson, RolfLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)farm-rha
(author)
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Samuelson, LC
(author)
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Rehfeld, JF
(author)
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Friis-Hansen, L
(author)
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Institutionen för experimentell medicinsk vetenskapMedicinska fakulteten
(creator_code:org_t)
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In:Gastroenterology: Elsevier BV126:2, s. 476-4871528-00120016-5085
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