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1999 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 10470145
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

MIYASAKA Kyoko  Tokyo Metro. Inst. Gerontol. Head of Dept. Clin. Physiol., 臨床生理部門, 研究室長 (90166140)

Co-Investigator(Kenkyū-buntansha) MASUDA Masao  Assistant Researcher of Dept. Clin. Physiol., 臨床生理部門, 助手 (20260284)
Project Period (FY) 1998 – 1999
KeywordsCCK / CCK receptor / CCK-A receptor / CCK-B receptor / pancreas / gene / gene expression / bile
Research Abstract

In humans, CCK has been known to stimulate pancreatic enzyme secretion via CCK-A receptors. Nevertheless, it was recently reported that gene expression of CCK-A receptor in the human pancreas could not be detected by Northen blot analysis. In the present study, we examined the mechanism of regulation of human pancreas by CCK and compared with those in mice and rats.
Any dose of CCK could not stimulate amylase release from the human pancreatic dispersed acini, whereas GRP and acetylsholine did. The amylase release stimulated by acetylcholein and GRP were inhibited by atropine and a GRP antagonist, respectively. CCK-A receptor gene expression was not detected by Northern blot analysis but CCK-B receptor gene expression was detected in the human pancreas. Autoradiography using aィイD1125ィエD1-CCK-8 revealed positive binding sites in the human pancreas and these bindings were replaced by a CCK-B receptor antagonist but not by a CCK-A receptor antagonist. 1ィイD1125ィエD1-CCK-8 also bound human duo … More denum and was replaced by CCK-A receptor antagonist. Therefore, we confirmed that CCK-B receptors, not A receptors, were rich in human pancreas and that CCK did not stimulate amylase release from the acinar cells, directly.
In rats, vagal afferent nerves in the stomach was responsible for CCK and the excitation was blocked by CCK-A receptor antagonist, not by B receptor antagonist. Taken together, it is interpreted that CCK stimulated human pancreas via vagal afferent nerve and passing through the vagal complex in the brain (vago-vagal reflex).
The bile and pancreatic juice secretion were examined in CCD-B receptor gene knockout mice. The lack of CCK-B receptor did not modify these secretions, or pancreatic growth. Thus, CCK-B receptor is not mandatory for the bile and pancreatic secretion or other regulation may compensate CCK-B receptor function. The CCK-A receptor gene knockout mice have been generated. They shows normal growth and are fertile. The bile and pancreatic juice secretion were not stimulated by CCK but were responsible for other stimulants such as GRP and acetylcholine. The pancreatic wet weight was not different among three genotypes. In rats, CCK-A receptor gene expression has been known to appear after birth. We reported this gene expression was correlated with demthylation. Less

  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Funakoshi A: "Lack of appropriate citation"J. Gastroenterol.. 34. 296-296 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyasaka K: "Disruption of cholecysokinin(CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic groeth. A study in CCK-A receptor gene knockout mice"Pancreas. 19. 114-118 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeshi K: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization"Biochem cell Biol. 77. 223-228 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyasaka K: "Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats : A study in naturally occurring CCK-A receptor gene knockout rats"Pancreas. 19. 217-223 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsusue K: "Expression of cholecysokinin type A receptor gene correlates with DNA demethlation during postnatal development of rat pancreas"Biochem Biophys Rea Comm. 264. 29-32 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanami T: "Different effects of trypsin inhibitors on intestinal gene expression of secretin nad on pancreatic bicarbonate secretion in CCK-A receptor dificicent rats"Jpn J Pharmacol. 81. 2339-2345 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki S: "Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats"Pancreas. 20. 94-101 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] Funakoshi A: "Body fat content is related to cholecysokinin A receptor gene promotor polymophism"Pancreas. 466. 264-266 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanami T: "Oral administration of a synthetic trypsin inhibitor increases pancreatic duct function in CCK-A receptor-deficient rats"Pancreas. (in press).

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      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi H: "Lymphatic lipid transport is not impaired in aging rats intestine"Mech Development A ging. (in press).

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      「研究成果報告書概要(和文)」より
  • [Publications] 宮坂京子: "加齢と消化吸収。"化学と生物. 37. 368-374 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 宮坂京子: "コレシストキニン(CCK)と膵機能。"総合臨床. 48. 1649-1656 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 船越顕博: "CCK-A受容体遺伝子の構造以上と疾病"消化器科. 28. 598-605 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 宮坂京子: "老化促進因子の発症機序の解明-ことに肥満、成人型糖尿病の発症と行動以上とコレシストキニン(CCK)-A-レセプター遺伝子以上の関連。第40回日本老年医学会学術集会記録<ノバルティス老化および老年医学研究基金1996年ど受賞者講演>"日本老年医学会雑誌. 36. 90-94 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Funakoshi A: "Obesity and NIDDM"Shima K. 248 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Jimi A: "Obesity and NIDDM"Shima K. 248 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi S: "Obesity and NIDDM"Shima K. 248 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Miyasaka K, Kanai S, Ohta M, Jimi A, Kono A, Funakoshi A.: "Overexpression of cholecystokinin (CCK)-B/gastrin receptor gene in the stomach of naturally occurring CCK-A receptor gene knockout rats."Digestion. 59. 26-32 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Masuda M., Kanai S., Miyasaka K.: "Inhibitory effect of central dopamine on basal pancreatic secretion."Am. J. Physiol.. 274. G29-34 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K., Ohta M., Tateishi K., Jimi A., Funakoshi A.: "Role of cholecystokinin (CCK)-A receptor in pancreatic regeneration after pancreatic duct occlusion: A study in rats lacking CCK-A receptor gene expression."Pancreas. 16. 114-123 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Takiguchi S., Takata Y., Takahashi N., Kataoka K., Hirashima T., Kawano K., Miyasaka K., Funakoshi A., Kono A.: "A disrupted cholecystokinin A receptor gene acted synergistically with ODB-1 gene to diabetic in obese rats."Am. J. Physiol.. 274. E265-270 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K., Jimi A, Kanai S, Sato Y, Masuda M, Ohta M, Funakoshi A.: "Incidence of apoptosis in the pancreas of young and old rats."Arch. Gerontol. Geriatr.. 26. 235-245 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ichikawa M, Miyasaka K, Fujita Y, Shimazoe T, Funakoshi A.: "Disappearance of dirunal rhythm of energy expenditure in genetically diabetic obese rats."Jpn J Physiol. 48. 211-214 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K, Funakoshi A.: "Luminal feedback regulation, monitor peptide, CCK-releasing peptide, and CCK receptors."Pancreas. 16. 277-283 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K, Kanai S, Masuda M, Funakoshi A.: "Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats."J Auton Nerv Syst. 73. 277-283 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Funakoshi A, Fukamizu Y, Miyasaka K.: "Mechanism of cholecystokinin-A receptor antagonist on human pancreatic exocrine secretion: Localization of CCK-A receptor in the human duodenum."Digestion. 60(suppl 1). 75-80 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K, Tateishi K, Masuda M, Jimi A, Funakoshi A.: "Atropine-resistant secretion of a putative luminal cholecystokinin releasing peptide in conscious rats."Am J Physiol. 276. G287-292 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kurosawa M, Buchinskaite V, Taniguchi T, Miyasaka K, Funakoshi A, Lungeberg T.: "Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors."J Auton Nerv Syst. 75. 51-59 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto S, Miyake M, Ohta M, Funakoshi A, Miyasaka K.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors."Physiol & Behav. 66. 869-872 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Shimazoe T, Maetani M, Nakamura S, Yamanouchi S, Watanabe S, Miyasaka K, Kono A, Funakoshi A,: "Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats."Jpn J Pharmacol. 80. 85-88 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K, Shinozaki H, Suzuki S, Sato Y, Kanai S, Masuda M, Jimi A, Nagata A, Matsui T, Noda T, Kono A, Funakoshi A.: "Disruption of cholecysotkinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth. A study in CCK-A receptor gene knockout mice."Pancreas. 19. 114-118 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tateishi K, Misumi Y, Ikehara Y, Miyasaka K, Funakoshi A.: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization."Biochem Cell Biol. 77. 223-228 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyasaka K, Suzuki S, Kanai S, Masuda M, Funakoshi A.: "Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats : A study in naturally occurring CCK-A recepter gene knockout rats."Pancreas. 19. 217-223 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsusue K, Takiguchi S, Takata Y, Funakoshi A, Miyasaka K, Kono A.: "Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas."Biochem Biophys Res Comm. 264. 29-32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawanami T, Suzuki S, Yoshida Y, Kanai S, Takata Y, Shimazoe T, Watanabe S, Funakoshi A, Miyasaka K.: "Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A receptor deficient rats."Jpn J Pharmacol. 81. 2339-345 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukakoshi A, Miyasaka K, Yamamori S, Takata Y, Kataoka K, Takiguchi S, Kono A, Shimokata H.: "Body fat content is related to cholecystokinin A receptor gene promotor polymorphism"FEBS Lett. 466. 264-266 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Funakoshi A, Takiguchi S, Takata Y, Kono A, Miyasaka K.: "Disrupted cholecystokinin type-A receptor gene in OLETF rats."Obesity and NIDDM. Edited by Shima K. Elsevier. 87-98 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jimi A, Miyasaka K, Shinozaki H, Funakoshi A.: "Morphological changes in the pancreatic islets of the OLETF rats."Obesity and NIDDM. Edited by Shima K. Elsevier. 87-98 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi S, Miyasaka K, Funakoshi A.: "Behavior abnormalities in the OLETF rats."Obesity and NIDDM. Edited by Shima K. Elsevier. 87-98 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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