Document Detail

Genetic dissection of the signaling pathways that control gastric acid secretion.
MedLine Citation:
PMID:  16259739     Owner:  NLM     Status:  MEDLINE    
Gastric acid secretion is regulated by endocrine, paracrine and neurocrine signals via at least three pathways, the gastrin-histamine pathway, the CCK-somatostatin pathway and the neural pathway. Genetically-engineered mice, subjected to targeted gene disruption (i.e., knockout mice), have been used to dissect the signaling pathways that are responsible for the complexity of the regulation of acid secretion in vivo. Both gastrin knockout and gastrin/CCK2 receptor knockout mice displayed greatly impaired acid secretion, presumably because of the loss of the gastrin-histamine pathway. Gastrin/CCK double-knockout mice had a relatively high percentage of active parietal cells with a maintained ability to respond with copious acid secretion to pylorus ligation-evoked vagal stimulation and to a histamine challenge. The low acid secretion in gastrin knockout mice and gastrin/CCK2 receptor knockout mice and the restoration of acid secretion in gastrin/CCK double-knockout mice suggest that CCK plays an important role as inhibitor of the parietal cells via the CCK-somatostatin pathway by stimulating the CCK1 receptor of the D cell. In the absence of both the gastrin-histamine and the CCK-somatostatin pathway (as in gastrin/CCK2 receptor double-knockout mice), the control of acid secretion is probably taken over by neural pathways, explaining the high acid output. The observations illustrate the complexity and plasticity of the acid regulatory mechanisms. It seems that one pathway may be suppressed or allowed to dominate over the others depending on the circumstances.
Duan Chen; Lennart Friis-Hansen; Rolf Håkanson; Chun-Mei Zhao
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Inflammopharmacology     Volume:  13     ISSN:  0925-4692     ISO Abbreviation:  Inflammopharmacology     Publication Date:  2005  
Date Detail:
Created Date:  2005-11-01     Completed Date:  2006-04-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112626     Medline TA:  Inflammopharmacology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  201-7     Citation Subset:  IM    
Department of Surgery, University Hospital Trondheim, Olav Kyrres gate 17, 7006 Trondheim, Norway.
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MeSH Terms
Gastric Acid / secretion*
Gastrins / genetics,  physiology*
Mice, Knockout
Models, Biological
Receptor, Cholecystokinin B / genetics,  physiology*
Signal Transduction / physiology*
Reg. No./Substance:
0/Gastrins; 0/Receptor, Cholecystokinin B

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