| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Cholecystokinin(CCK) is a peptide hormone that has important physiological functions. Recently, CCK-A and -B receptor(R)s were cloned. Species differences in the pancreatic expression of CCK-Rs have been reported. Gene expression of CCK-AR was detected in human gallbladder, but not in human pancreas. In mammals including humans, CCK mediates satiety effect via CCK-AR. We examined whether gastric emptying of a nonnutrient liquid load was modified in CCK-AR, BR, and ARBR gene knockout mice. Gastric emptying was significantly enhanced in mice lacking CCK-BR, as compared with wild-type and CCK-AR(-/-) mice. CCK-8S inhibited gastric emptying in mice with CCK-AR, but not in mice without CCK-AR. A proton pump inhibitor did not affect gastric emptying. Atropine dose dependently inhibited gastric emptying in all genotypes. The thickness of smooth muscle was comparable for all genotypes. The gastric emptying of a nonnutrient liquid load was enhanced in mice without CCK-BR, although the precise m
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echanism is not known. Although cholecystokinin(CCK) has been shown to inhibit gastric emptying via CCK-A receptors(CCK-ARs), the role of CCK-B receptors(CCK-BRs) has not been verified. We examined whether gastric emptying of a nonnutrient liquid load was modified in CCK-AR, BR, and ARBR gene knockout mice.
We generated CCK-AR gene deficient(-/-) mice and found that the daily food intake, energy expenditure, and gastric emptying of a liquid meal were not changed, compared with wild-type mice. As CCK-AR(-/-) mice showed a anxiolytic status, we examined the changes in daily food intake after the swimming stress or after the restraint stress. Five-minute swimming for 3 days did not modify the changes in body weight and daily food intake between the two genotypes. Seven-h restraint stress significantly decreased body weight as well as food intake during subsequent 3 days. Then, on the fourth day, food intake increased in both genotypes. CCK-AR(-/-) mice showed a significantly higher level than the value before restraint stress. However, the food intake was only recovered to the level before the stress in wild-type mice. This evidence suggested that the CCK-AR function might be involved in stress-induced hyperphagia. Less
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