Document Detail

Gastric acid secretion in cholecystokinin-1 receptor, -2 receptor, and -1, -2 receptor gene knockout mice.
MedLine Citation:
PMID:  19340558     Owner:  NLM     Status:  MEDLINE    
Gastrin is important for stimulating acid secretion as well as differentiating gastric mucosal cells via cholecystokinin-2 receptors (CCK-2Rs). In turn, CCK acts preferably via CCK-1R to release somatostatin, and somatostatin has been postulated to exhibit a tonic inhibition of gastrin bioactivity. The present study was designed to examine the hypothesis that CCK-1R and 2R may act in opposite directions in gastric acid secretion. Having generated CCK-1R(-/-), 2R(-/-), and 1R(-/-)2R(-/-) mice, we examined the regulation of gastric acid secretion in four genotypes including wild-type mice. Parietal cells possess histamine receptors, muscarinic receptors, and CCK-2Rs. Since histamine increases cAMP and carbachol increases calcium, the responses of gastric acid secretion to graded doses of histamine, carbachol, and a combination of histamine + carbachol were determined. The sensitivity to histamine did not differ among the four genotypes, while the maximal acid secretion was lower in CCK-2R(-/-) mice than in wild-type mice. In addition, sensitivity to carbachol was impaired in mice without CCK-2R. The interaction of histamine and carbachol was conserved in all genotypes. In conclusion, CCK-2R is necessary to respond to carbachol as well as to produce the maximal acid secretion, while the role of CCK-1R in acid secretion is less important.
Setsuko Kanai; Hiroko Hosoya; Saeko Akimoto; Minoru Ohta; Toshimitsu Matsui; Soichi Takiguchi; Akihiro Funakoshi; Kyoko Miyasaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-30
Journal Detail:
Title:  The journal of physiological sciences : JPS     Volume:  59     ISSN:  1880-6546     ISO Abbreviation:  J Physiol Sci     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262417     Medline TA:  J Physiol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  23-9     Citation Subset:  IM    
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan.
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MeSH Terms
Acetylcholine / metabolism
Carbachol / pharmacology
Cholecystokinin / metabolism
Cholinergic Agonists / pharmacology
Gastric Acid / metabolism,  secretion*
Gastric Mucosa / drug effects,  metabolism,  secretion
Histamine / pharmacology
Histamine Agonists / pharmacology
Mice, Inbred C57BL
Mice, Knockout
Receptor, Cholecystokinin B / genetics*,  metabolism*
Receptors, Cholecystokinin / genetics*,  metabolism*
Reg. No./Substance:
0/CCK1 protein, mouse; 0/Cholinergic Agonists; 0/Histamine Agonists; 0/Receptor, Cholecystokinin B; 0/Receptors, Cholecystokinin; 51-45-6/Histamine; 51-83-2/Carbachol; 51-84-3/Acetylcholine; 9011-97-6/Cholecystokinin

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