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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

Research Project

Project/Area Number 13670077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

KANAI Setuko  Tokyo Metro. Inst. Gerontol. Head of Dept. Clin. Physiol., ASSISTANTS RESEARCHER, 東京都老人総合研究所・生体機能調節と加齢グループ, 研究助手 (90100122)

Co-Investigator(Kenkyū-buntansha) MIYASAKA Kyouko  Tokyo Metro. Inst. Gerontol. Head of Dept. Clin. Physiol., HEAD, 福祉振興財団東京都老人総合研究所・生体機能調節と加齢グループ, グループリーダー (90166140)
増田 正雄  東京都老人総合研究所, 臨床生理部門, 研究助手 (20260284)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsCCK receptor / CCK-B receptor / CCK-A receptor / pancreas / gene / gene expression / gallstone / CCK-A受容体KOマウス / CCK-B受容体KOマウス / CCK-A, B受容体ダブルKOマウス
Research Abstract

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-BR
3. 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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Suzuki S, Takiguchi S, Sato N, Kanai S, Miyasaka K, Funakoshi: "Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion : A study in CCK-A receptor knockout mice"Jpn J Physiol. 51. 585-590 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takiguchi S, Suzuki S, Sato Y, Kanai S, Miyasaka K: "Role of CCK-A receptor for pancreatic function in mice : A study in CCK-A receptor knockout mice"Pancreas. 24. 276-283 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Ichikawa M, Ohta M, Kanai S, Yoshida Y, Masuda: "Increased energy metabolism and energy turnover in mice lacking cholecystokinin-B receptor"J Nutr. 132. 739-741 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N, Suzuki S, Kanai S, Ohta M., Funakoshi A, Miyasaka K: "Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin (CCK)-A receptor gene knockout mice and wild type mice"Jpn J Pharm. 89. 290-295 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Masuda M, kanai S, Sato N, Kurosawa M: "Central orexin-A stimulates pancreatic exocrine secretion via vagus"Pancreas. 25. 400-404 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Kobayashi S, Ohta M, kanai S, Yoshida Y, Nagata: "Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze"Neurosci Lett. 335. 115-118 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Ichikawa M, Kawanami T, Kanai S, Ohta M, Sato N, Ebisawa H, Funakoshi A: "Physical activity prevented age-related decline in energy metabolism in genetically obese and diabetic rats, but not in control rats"Mech Aging and Develop. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Funakoshi A: "Cholecystokinin and cholecystokinin receptors"A review article J Gastroenterol. 38. 1-13 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takiguchi S, Takata Y, Kawanami T, Funakoshi A: "Anxiety-related behaviors in cholecystokinin-A,B, and AB receptor gene knockout mice in the plus-maze"Neurosci Lett. 335. 115-118 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi H, Sato Y, Kanai S, Ichikawa M, Funakoshi a, Miyasaka K: "Increased lymphatic lipid transport in genetically diabetic obese rats"Am J Physiol. 282. G69-76 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Masuda M, Kanai S, Ohta M, Suzuki S, Tateishi K, Funakoshi A: "Inhibitory effects of octreotide on luminal CCK releasing factor, plasma CCK, and pancreatic secretion in conscious rats"Pancreas. 24. 269-275 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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. 24. 276-283 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida Y, Ichikawa M, Ohta M, Kanai S, Kobayashi M, Ichimaru Y, Shimazoe T, Watanabe S, Funakoshi A, Miyasaka K: "A PPARg agonist influenced daily profile of energy expenditure in genetically obese diabetic rats"Jpn J Pharm. 88. 279-184 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Shinozaki H, Jimi A, Funakoshi A: "Amylase secretion from dispersed human pancreatic acini : Neither CCK-A nor CCK-B receptors mediate amylase secretion in vitro"Pancreas. 25. 161-165 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Ichikawa M, Ohta M, Kanai S, Yoshida Y, Masuda M, Nagata A, Matsui T, Noda T, Takiguchi S, Takata Y, Kawanami T, Funakoshi A: "Increased energy metabolism and energy turnover in mice lacking cholecystokinin-B receptor"J Nutr. 132. 739-741 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takata Y, Takeda S, Kawanami T, Takiguchi S, Yoshida Y, Miyasaka K, Funakoshi A: "Promoter analysis of human cholecystokinin (CCK) type-A receptor gene"J Gastroenterol. 37. 815-820 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N, Suzuki S, Kanai S, Ohta M, Jimi A, Noda T, Takibuchi S, Funakoshi A, Miyasaka K: "Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin (CCK)-A receptor gene knockout mice and wild type mice"Jpn J Pharm. 89. 290-295 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Masuda M, Kanai S, Sato N, Kurosawa M, Funakoshi A: "Central orexin-A stimulates pancreatic exocrine secretion via vagus"Pancreas. 25. 400-404 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Takata Y, Funakoshi A: "Association of cholecystokinin A receptor gene polymorphism with cholelithiasis and its molecular mechanisms"J Gastroenterol. 37 (suppl). 102-106 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Carrillo MC, Kanai S, Miyasaka K, Kitani K: "A protein free diet uncovers the potential age-difference in the heOpatic detoxifying system, glutathione S-transferase, in female mice"Mech Aging and Develop. 132. 1617-1623 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kurosawa M, Iijima S, Funakoshi A, Kawanami T, Miyasaka K, Bucinskaite V, Lundeberg T: "Cholecystokinin-8 (CCK-8) has no effect on heart rate in rats lacking CCK-A receptors"Peptides. 22. 1279-1284 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Masuda M, Kanai S, Ohta M, Suzuki S, Tateishi K, Funakoshi A: "Inhibitory effect of somatostatin on CCK release is independent of luminal LCRF content in conscious rats"Pancreas. 23. 414-420 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki S, Takiguchi S, Sato N, Kanai S, Kawanami T, Yoshida Y, Miyasaka K, Takata Y, Funakoshi A, Noda T: "Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion : A study in CCK-A receptor knockout mice"Jpn J Physiol. 51. 585-590 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyasaka K, Ichikawa M, Ohta M, Kanai S, Yoshida Y, Masuda Funakoshi A, Miyasaka K: "Increased energy metabolism and energy turnover in mice lacking cholecystokinin-B receptor"J Nutr. 132. 739-741 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato N, Suzuki S, Kanai S, Ohta M, Funakoshi A, Miyasaka K: "Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin (CCK)-A receptor gene knockout mice and wild type mice"Jpn J Pharm. 89. 290-295 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyasaka K, Masuda M, Kanai S, Sato N, Kurosawa M: "Central orexin-A stimulates pancreatic exocrine secretion via vagus"Pancreas. 25. 400-404 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takiguchi: "Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze"Neurosci Lett. 335. 115-118 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pancreas. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki S, Takiguchi S. Kanai S, Miyasaka K: "Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion : A study in CCK-A receptor knockout mice."Jpn J Physiol,. 51. 585-590 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takiguchi S, Suzuki S, Kanai S, Ichimarn Y, Funakoshi A, Miyasaka K: "Role of CCK-A receptor for pancreatic unction in mice : A study in CCK-A receptor knockout mice."Pancreas. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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