生体機能調節におけるコレシストキニン(CCK)-A,-B受容体の機能分担と遺伝子の発現 副題:自然発症CCK-A受容体欠損ラット、CCK-A,-B受容体遺伝子ターゲティングマウスによる検討

已经确定了两种类型的CCK受体（A型和B型）。我们培养CCK-A，-B和AB受体敲除小鼠，测定这些受体在胃功能和胆胰分泌中的作用。缺乏CCK-BR的小鼠基底胃酸分泌减少。给药胃泌素和组胺显著增加了所有基因型的酸分泌。缺乏CCK-BR增强胃排空液体负荷。CCK- ar小鼠胃排空被CCK抑制，而非CCK- ar小鼠胃排空无抑制作用。然而，在所有基因型中，阿托品都能抑制胃排空，需要更大的剂量才能在CCK-BR小鼠中显示出与非CCK-BR小鼠相似的效果。因此，自主神经功能可能因CCK-BR3缺失而改变。我们证实CCK不会诱导CCK- ar（-/-）小鼠胆囊收缩和胰淀粉酶分泌。其他兴奋剂如乙酰胆碱和神经素C可刺激CCK-AR（-/-）小鼠的淀粉酶分泌，但不能引起胆囊收缩。分泌素不能增加小鼠的碳酸氢盐分泌，而CCK通过CCK- a受体增加小鼠的碳酸氢盐分泌。CCK-AR（-/-）小鼠的糖耐量没有改变。在CCK-AR（-/-）小鼠中，高蛋白和高脂肪的饮食可以诱导年龄相关的胆结石形成，但在野生型小鼠中则没有。没有CCK-BR的小鼠在正迷宫中的焦虑相关行为增加。

Two types of CCK receptors (type A and type B) have been identified. We raised CCK-A,-B and AB receptor knockout mice, the role of these receptors in gastric functions and bile-pancreatic secretions was determined.1. Basal gastric acid secretion was decreased in mice lacking CCK-BR. Administration of gastrin and histamine significantly increased acid secretion in all genotypes.2. Lack of CCK-BR enhanced gastric emptying of a liquid load. The gastric emptying was inhibited by administration of CCK in mice with CCK-AR, but not in mice without CCK-AR. Atropine inhibited gastric emptying in all genotypes, however, larger doses were required to reveal a similar effect in mice with CCK-BR to in mice without CCK-BR. Therefore, autonomic nerve functions might be altered by the lack of CCK-BR3. We confirmed that CCK did not induce gallbladder contraction nor pancreatic amylase secretion in CCK-AR(-/-) mice. Other stimulants such as acethocholine and neuromedin C could stimulated amylase secretion in CCK-AR(-/-) mice but could not produce gallbladder contraction. Secretin failed to increase bicarbonate secretion in mice, and CCK increased bicarbonate secretion via CCK-A receptor in mice. Glucose tolerance was not altered in CCK-AR(-/-) mice.4. Age associated gallstone formation was induced by administration of a higher protein and fat diet in CCK-AR(-/-) mice, but not in wild type mice.5. Anxiety related behaviors in the plus maze were increased in mice without CCK-BR.