Lack of Ghrelin Secretion in Response to Fasting in Cholecystokinin-A (-1), -B (-2) Receptor–Deficient Mice

The Journal of Physiological Sciences

Akihiro Funakoshi³  Hiroshi Uematsu¹  Kyoko Miyasaka²  Setsuko Kanai²  Chihiro Sakurai²  Minoru Ohta² 

[1] Department of Gerodontology, Division of Gerontology and Gerodontology, Graduate School, Tokyo Medical and Dental University;Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology;Department of Gastroenterology, Kyushu Cancer Center

关键词: CCK-A (1) receptor;    CCK-B (2) receptor;    ghrelin;    food intake;    knockout mice;   

DOI  :  10.2170/physiolsci.RP003306

学科分类：生理学

来源: Springer

【 摘 要 】

References(39)Cited-By(3)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.

【 授权许可】

Unknown