Document Detail


Lack of ghrelin secretion in response to fasting in cholecystokinin-A (-1), -B (-2) receptor-deficient mice.
MedLine Citation:
PMID:  17134539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholecystokinin receptors (CCK-Rs) have been classified into two subtypes: CCK-AR (1R) and -BR (2R). We generated CCK-AR(-/-), CCK-BR(-/-), and CCK-AR(-/-)BR(-/-) mice and found that the gastric emptying of a liquid meal was increased in CCK-BR(-/-) and AR(-/-)BR(-/-) mice, compared with wild-type and CCK-AR(-/-) mice. Given that enhanced gastric emptying leads to eating, food intake after overnight fasting was examined, as was the effect of CCK-8S on food intake. Male mice 6-8 months of age were deprived of food for 16 h with free access to water, after which they were injected intraperitoneally (0.1 ml/mouse) with either vehicle or CCK-8 (0.3, 1.0, or 3.0 nmol/mouse), and their food intake was monitored for 4 h. CCK-8S inhibited food intake in wild-type and CCK-BR(-/-) mice, but not in CCK-AR(-/-) or AR(-/-)BR(-/-) mice. Unexpectedly, we observed a lower food intake in CCK-AR(-/-)BR (-/-) mice treated with vehicle than in mice of the other genotypes. To examine the mechanism of decrease in food intake in CCK-AR(-/-)BR(-/-) mice, the involvement of ghrelin was determined in wild-type and CCK-AR(-/-)BR(-/-) mice. Fasting plasma ghrelin levels were significantly lower in CCK-AR (-/-)BR(-/-) mice than in wild-type mice, and no increase in response to fasting was observed in CCK-AR(-/-)BR(-/-) mice. An administration of acyl-ghrelin produced a small increase in food intake in CCK-AR(-/-)BR(-/-) mice, but not to the levels of wild-type mice. In conclusion, CCK-AR(-/-)BR(-/-) mice showed lower food intake as well as lower response to exogenous ghrelin, and a lower plasma ghrelin level after fasting, though which receptor is more important is unknown.
Authors:
Chihiro Sakurai; Minoru Ohta; Setsuko Kanai; Hiroshi Uematsu; Akihiro Funakoshi; Kyoko Miyasaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-01
Journal Detail:
Title:  The journal of physiological sciences : JPS     Volume:  56     ISSN:  1880-6546     ISO Abbreviation:  J Physiol Sci     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-27     Completed Date:  2007-04-03     Revised Date:  2008-12-29    
Medline Journal Info:
Nlm Unique ID:  101262417     Medline TA:  J Physiol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  441-7     Citation Subset:  IM    
Affiliation:
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015 Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Eating / drug effects,  physiology
Fasting / metabolism*
Gastric Emptying / physiology
Ghrelin
Male
Mice
Mice, Knockout
Nootropic Agents / pharmacology
Peptide Hormones / physiology,  secretion*
Receptor, Cholecystokinin A / genetics,  metabolism*
Receptor, Cholecystokinin B / genetics,  metabolism*
Sincalide / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/8-sulfocholecystokinin octapeptide; 0/Ghrelin; 0/Nootropic Agents; 0/Peptide Hormones; 0/Receptor, Cholecystokinin A; 0/Receptor, Cholecystokinin B; 25126-32-3/Sincalide

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