CCK-A,B両受容体欠損マウスの血中および胃内グレリン濃度低下

抄録

In mammals including humans, a brain-gut hormone, cholecystokinin (CCK) mediates the satiety effect via CCK-A receptor (R). However, we generated CCK-AR gene deficient (-/-) mice and found that the daily food intake, energy expenditure, and gastric emptying did not change compared with those of wild-type mice. We also generated CCK-BR (-/-), CCK-AR (-/-) BR (-/-) mice. Daily food intake and ghrelin contents in the blood and the stomach were investigated. Male mice at 6-8 months of age were used. Mice, deprived of food for 18 hr with free access to water, were injected i.p. (0.1ml/mouse) with either vehicle or CCK-8 (0.3, 1.0, and 3.0 n mol/mouse). Thereafter, daily food intake was measured. Additional animals were sacrificed by guillotine, the blood was obtained, and the stomach was removed to measure ghrelin contents. Administration of CCK-8S significantly decreased food intake in wild-type and in CCK-BR (-/-) mice. However, no significant inhibition was observed in CCK-AR (-/-) and in CCK-AR (-/-) BR (-/-) mice. When mice injected with vehicle were compared, food intake in CCK-AR (-/-) BR (-/-) mice was significantly lower than that in wild-type and CCK-BR (-/-) mice. Moreover, the ghrelin contents in the blood as well as in the stomach were significantly lower in CCK-AR (-/-) BR (-/-) mice than wild-type mice. CCK-Rs may be involved in the regulation of ghrelin biosynthesis and secretion. [J Physiol Sci. 2006;56 Suppl:S77]