Respective roles of CCK-A and B receptors in the regulation

CCK-A和B受体各自的调节作用

• 批准号: 12670100
• 负责人: OHTA Minoru
• 金额: $ 2.18万
• 依托单位: Tokyo Metropolitan Institute of Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670100/
• 关键词: CCK; CCK-A receptor; CCK-B receptor; Gastric emptying; knokout mice; gene; gene expression; CCK-A受容体ノックアウトマウス; CCK-B受容体ノックアウトマウス; CCK-AB受容体ノックアウトマウス

Cholecystokinin (CCK) is an important gastrointestinal hormone as well as neurotransmitter. Two types of CCK receptors (type A and type B) have been identified. The CCK-A receptor is known to be involved in satiety, food intake and behavior and the B receptor to be involved in anxiety. As we recently raised CCK-A, -B and AB receptor knockout mice, the role of these receptors was determined.CCK-BR(-/-) and AR(-/-)BR(-/-) mice showed increased anxiety states compared with CCK-AR(+/+)BR(+/+) and AR(-/-) mice. Previous reports showed that panic attack and anxiety could be induced by CCK-4, which predominantly bound CCK-BR. Our observation was not compatible for the previous report. Further study is necessary.The daily energy intake and energy expenditure were significantly higher in CCK BR(-/-) and CCK-AR(-/-)BR(-/-) mice than CCK-AR(-/-) and wild-type [CCKAR(+/+)BR(+/+)] mice. The ratios of liver and kidneys per body weight (g-kg) were significantly higher in CCKAR(-/-)BR(-/-) mice than wild-type mice. Energy metabolism and energy turnover were increased under the condition of disruption of CCK-BR gene, although the real mechanism is unknown.Gastric emptying was not delayed in CCK-AR(-/-) mice. Gastric emptying was enhanced in CCK-BR(-/-) and AR(-/-)BR(-/-) mice. However, administration of atropine significantly inhibited gastric emptying in all mice. CCK-8 delayed gastric emptying in CCK-AR(+/+)BR(+/+) and BR(-/-) mice, but not in CCK-AR(-/-) and AR(-/-)BR(-/-) mice.In mice, CCK, acetylcholine, and GRP could stimulate amylase release from the pancreas, whereas only CCK could induce gallb ladder contration.

胆囊收缩素（CCK）是一种重要的胃肠激素和神经递质。已鉴定出两种类型的CCK受体（A型和B型）。已知CCK-A受体与饱腹感、食物摄入和行为有关，而B受体与焦虑有关。我们最近饲养了CCK-A、-B和AB受体敲除小鼠，确定了这些受体的作用，CCK-BR（-/-）和AR（-/-）BR（-/-）小鼠与CCK-AR（+/+）BR（+/+）和AR（-/-）小鼠相比，表现出更高的焦虑状态。以往的研究表明，CCK-4主要与CCK-BR结合，可引起惊恐发作和焦虑。我们的观察结果与上一份报告不一致。CCK BR（-/-）和CCK-AR（-/-）BR（-/-）小鼠的每日能量摄入和能量消耗显著高于CCK-AR（-/-）和野生型[CCKAR（+/+）BR（+/+）]小鼠。CCKAR（-/-）BR（-/-）小鼠的肝脏和肾脏/体重比（g-kg）显着高于野生型小鼠。CCK-BR基因敲除可增加能量代谢和能量周转，但其真实的机制尚不清楚，CCK-AR（-/-）小鼠胃排空无延迟。CCK-BR（-/-）和AR（-/-）BR（-/-）小鼠胃排空增强。然而，阿托品给药显著抑制所有小鼠的胃排空。CCK-8可使CCK-AR（+/+）BR（+/+）和BR（-/-）小鼠胃排空延迟，但对CCK-AR（-/-）和AR（-/-）BR（-/-）小鼠胃排空无影响。

项目成果

Suzuki S, Miyasaka K, Jimi A, Funakoshi A.: "Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice."Pancreas. 21. 86-92 (2000)

Suzuki S、Miyasaka K、Jimi A、Funakoshi A.：“人 IL-6 基因转基因小鼠中雨蛙素诱导急性胰腺炎。”胰腺。

Shimokata H, Yamada Y, Nakagawa M, Okubo R, Saido T, Funakoshi A, Miyasaka K, Ohta S, Tsujimoto G, Tanaka M, Ando F, Niino N.: "Distribution of geriatric disease related genotypes in the National Institute of Longevity Sciences, Longitudinal Study of Angi

Shimokata H、Yamada Y、Nakakawa M、Okubo R、Saido T、Funakoshi A、Miyasaka K、Ohta S、Tsujimoto G、Tanaka M、Ando F、Niino N.：“国家长寿研究所老年疾病相关基因型的分布

Nomoto S., Miyake M., Ohta M., Funakoshi A.and Miyasaka K.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors."Physiol. & Behav.. 66. 869-872 (1999)

Nomoto S.、Miyake M.、Ohta M.、Funakoshi A. 和 Miyasaka K.：“没有胆囊收缩素 (CCK)-A 受体的 OLETF 大鼠的学习和记忆受损。”Physiol。

Suzuki S, Kanai S, Miyasaka K, Jimi A, Funakoshi A.: "Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats"Pancreas. 20. 94-101 (2000)

Suzuki S、Kanai S、Miyasaka K、Jimi A、Funakoshi A.：“意识大鼠短期导管闭塞期间迷走神经对胰腺分泌的调节”胰腺。

Takiguchi S, Suzuki S, Sato Y, Kanai S, Miyasaka K, Jimi A, Shinozaki H, Takata Y, Funakoshi A, Kono A, Minowa O, Kobayashi T, Noda T.: "Role of CCK-A receptor for pancreatic function in mice : A study in CCK-A receptor knockout mice"Pancreas. (in press).

Takiguchi S、Suzuki S、Sato Y、Kanai S、Miyasaka K、Jimi A、Shinozaki H、Takata Y、Funakoshi A、Kono A、Minowa O、Kobayashi T、Noda T.：“CCK-A 受体对胰腺功能的作用