1999 Fiscal Year Annual Research Report

膵外分泌調節におけるCCKと、CCK-A,CCK-B受容体遺伝子発現と機能分担副題:ヒトおよび自然発症CCK-A受容体欠損ラット、遺伝子ターゲティングマウスによる検討

Research Project

Project/Area Number	10470145
Research Institution	Tokyo Metropolitan Institute of Gerontology
Principal Investigator	宮坂京子財団法人東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)
Co-Investigator(Kenkyū-buntansha)	増田正雄財団法人東京都老人総合研究所, 臨床生理部門, 助手 (20260284)
Keywords	CCK / CCK受容体 / CCK-A受容体 / CCK-B受容体 / 膵臓 / 遺伝子 / 遺伝子発現調節 / 胆汁
Research Abstract	ヒトでは、CCKは膵酵素分泌を促し、これはCCK-A受容体拮抗剤によって阻害される。にもかかわらず、ヒト膵にはCCK-A受容体遺伝子発現は殆どみられない。ヒト膵は機能的にどちらの受容体が主体であるかを確認した。ヒト切除膵をコラーゲン処理し、遊離膵腺房細胞を作製し、刺激に対する反応をしらべた。10^<-12>-10^<-6>MCCK-8S刺激に対して、アミラーゼ分泌は全くおこらなかった。カルバコール、GRP刺激に対しては、用量依存製の分泌反応をしめし、GRP antagonistをもちいてGRP受容体の介在を証明した。ラット胃の迷走神経求心線維末端はCCKに感受性を有し、反応はA受容体拮抗剤で阻害された。ヒト十二指腸にはCCKの結合部位がありCCK-A受容体拮抗剤によってreplaceされた。CCK-AおよびCCK-B受容体遺伝子ノックアウトマウスでは、B受容体欠損は膵臓の機能、成長に、全く影響しないことがはっきりした。A受容体の欠損は、CCKに対する膵アミラーゼ分泌が欠落したが、その他の刺激には正常に反応し、膵臓の形態、成長に全く異常はみとめられなかった。

Research Products
(39 results)

All Other

All Publications (39 results)

[Publications] Miyasaka K.: "Overexpression of cholecystokinin (CCK)-B/gastrin receptor gene in the stomach of naturally occuuring CCK-A receptor gene knockout rat"Digestion. 59. 26-32 (1998)
[Publications] Masuda M.: "Inhibitory effect of central dopamine on basal pancreatic secretion"Am. J. Physiol.. 274. G29-34 (1998)
[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A receptor in pancreatic regeneration after pancreatic ductocclusion : A study in rats lacking CCK-A receptor gene expression"Pancreas. 16. 114-123 (1998)
[Publications] Takiguchi S.: "A disrupted cholecystokinin A receptor gene acted synergistically with ODB-1 gene to diabetic in obese rats"Am. J. Physiol.. 274. E265-270 (1998)
[Publications] Miyasaka K.: "Incidence of apoptosis in the pancreas of young and rats"Arch. Gerontol. Geriatr.. 26. 235-245 (1998)
[Publications] Ichikawa M.: "Disappearance of dirunal rhythm of energy expenditure in genetically diabetic obese rats"Physiol. 48. 211-214 (1998)
[Publications] Miyasaka K.: "Luminal feedback regulation,monitor peptide, CCK-releasing peptide,and CCK receptors"Pancreas. 16. 277-283 (1998)
[Publications] Miyasaka K.: "Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats"J Auton Nerv Syst. 73. 143-148 (1998)
[Publications] Funakoshi A.: "Mechanism of cholecystokinin-A receptor antagonist on human pancreatic exocrine secretion : Localization of CCK-A receptor in the human duodenum"Digestion. 60(suppl). 75-80 (1999)
[Publications] Miyasaka K.: "Atropine-resistant secretion of a putative luminal cholecystokinin releasing peptide in conscious rats"Am. J. Physiol.. 276. G287-292 (1999)
[Publications] Kurosawa M.: "Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors"J Auton Nerv Syst. 75. 51-59 (1999)
[Publications] Nomoto S.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors"Physiol & Behav. 66. 869-872 (1999)
[Publications] Shimazoe T.: "Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats"Jpn. J. Pharmacol. 80. 85-88 (1999)
[Publications] Funakoshi A.: "Lack of appropniate citation"J. Gastroenterol.. 34. 269-269 (1999)
[Publications] Miyasaka K.: "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)
[Publications] Tateishi K.: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization"Biochem Cell Biol.. 77. 223-228 (1999)
[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)
[Publications] Matsusue K.: "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)
[Publications] Kawanami T.: "Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A receptor deficicent rats"Jpn J Pharmacol. 81. 2339-2345 (1999)
[Publications] Suzuki S.: "Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats"Pancreas. 20. 94-101 (2000)
[Publications] Funakoshi A.: "Body fat content is related to cholecystokinin A receptor gene promotor polymorphism"FEBS Lett.. 466. 264-266 (2000)
[Publications] Kawanami T.: "Oral administration of a syntheric trypsin inhibitor increases pancreatic duct function in CCK-A receptor-deficient rats"(in press).
[Publications] Hayashi H.: "Lymphatic lipid transport is not impaired in aging rats intestine."(in press).
[Publications] 松永俊哉: "持久的運動トレーニングが急性運動負荷による血漿中消化管ホルモンの変動に及ぼす影響"体力研究. 95. 1-7 (1998)
[Publications] 自見厚郎: "ラット膵管結紮膵炎における膵管内投与膵分泌性トリプシンインヒビター(PSTI)の障害阻害効果"膵臓. 13. 25-31 (1998)
[Publications] 船越顕博: "膵炎の器質化、慢性化の病態解明とCamostat経口投与による進展阻止効果の基礎的研究"現代医療. 30. 143-147 (1998)
[Publications] 永松俊哉: "身体運動における負荷強度の違いが膵外分泌作用に及ぼす影響"消化と吸収. 21. 77-80 (1998)
[Publications] 宮坂京子: "図解病態のメカニズム、膵外分泌調節"medicina. 35. 161-165 (1998)
[Publications] 宮坂京子: "CCK受容体"生体の科学特集受容体. 49. 381-383 (1998)
[Publications] 船越顕博: "CCK-A受容体欠損ラットと摂食行動異常"Frontiers Gastroenterology. 3. 74-83 (1998)
[Publications] 宮坂京子: "加齢と消化吸収"化学と生物. 37. 368-374 (1999)
[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)
[Publications] 船越顕博: "CCK-A受容体遺伝子の構造異常と疾病"消化器科. 28. 598-605 (1999)
[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異常とコレシストキニン(CCK)-A-レセプター遺伝子異常の関連。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年度受賞者講演"日本老年医学会雑誌. 36. 90-94 (1999)
[Publications] Funakoshi A.: "Obesity and NIDDM"Shima K.. 248 (1999)
[Publications] Jimi A.: "Oresity and NIDDM"Shima K.. 248 (1999)
[Publications] Kobayashi S.: "Obesity and NIDDM"Shima K.. 248 (1999)
[Publications] 宮坂京子: "サクセスフルエイジング"東京都老人研(ワールドプラニング社). 303 (1998)
[Publications] 宮坂京子(分担): "臨床研修イラストライテッド消火器系マニュアル"羊土社. 197 (1998)

1999 Fiscal Year Annual Research Report

膵外分泌調節におけるCCKと、CCK-A,CCK-B受容体遺伝子発現と機能分担 副題:ヒトおよび自然発症CCK-A受容体欠損ラット、遺伝子ターゲティングマウスによる検討

Principal Investigator

宮坂 京子 財団法人 東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)

Research Products

[Publications] Miyasaka K.: "Overexpression of cholecystokinin (CCK)-B/gastrin receptor gene in the stomach of naturally occuuring CCK-A receptor gene knockout rat"Digestion. 59. 26-32 (1998)

[Publications] Masuda M.: "Inhibitory effect of central dopamine on basal pancreatic secretion"Am. J. Physiol.. 274. G29-34 (1998)

[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A receptor in pancreatic regeneration after pancreatic ductocclusion : A study in rats lacking CCK-A receptor gene expression"Pancreas. 16. 114-123 (1998)

[Publications] Takiguchi S.: "A disrupted cholecystokinin A receptor gene acted synergistically with ODB-1 gene to diabetic in obese rats"Am. J. Physiol.. 274. E265-270 (1998)

[Publications] Miyasaka K.: "Incidence of apoptosis in the pancreas of young and rats"Arch. Gerontol. Geriatr.. 26. 235-245 (1998)

[Publications] Ichikawa M.: "Disappearance of dirunal rhythm of energy expenditure in genetically diabetic obese rats"Physiol. 48. 211-214 (1998)

[Publications] Miyasaka K.: "Luminal feedback regulation,monitor peptide, CCK-releasing peptide,and CCK receptors"Pancreas. 16. 277-283 (1998)

[Publications] Miyasaka K.: "Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats"J Auton Nerv Syst. 73. 143-148 (1998)

[Publications] Funakoshi A.: "Mechanism of cholecystokinin-A receptor antagonist on human pancreatic exocrine secretion : Localization of CCK-A receptor in the human duodenum"Digestion. 60(suppl). 75-80 (1999)

[Publications] Miyasaka K.: "Atropine-resistant secretion of a putative luminal cholecystokinin releasing peptide in conscious rats"Am. J. Physiol.. 276. G287-292 (1999)

[Publications] Kurosawa M.: "Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors"J Auton Nerv Syst. 75. 51-59 (1999)

[Publications] Nomoto S.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors"Physiol & Behav. 66. 869-872 (1999)

[Publications] Shimazoe T.: "Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats"Jpn. J. Pharmacol. 80. 85-88 (1999)

[Publications] Funakoshi A.: "Lack of appropniate citation"J. Gastroenterol.. 34. 269-269 (1999)

[Publications] Miyasaka K.: "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)

[Publications] Tateishi K.: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization"Biochem Cell Biol.. 77. 223-228 (1999)

[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)

[Publications] Matsusue K.: "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)

[Publications] Kawanami T.: "Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A receptor deficicent rats"Jpn J Pharmacol. 81. 2339-2345 (1999)

[Publications] Suzuki S.: "Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats"Pancreas. 20. 94-101 (2000)

[Publications] Funakoshi A.: "Body fat content is related to cholecystokinin A receptor gene promotor polymorphism"FEBS Lett.. 466. 264-266 (2000)

[Publications] Kawanami T.: "Oral administration of a syntheric trypsin inhibitor increases pancreatic duct function in CCK-A receptor-deficient rats"(in press).

[Publications] Hayashi H.: "Lymphatic lipid transport is not impaired in aging rats intestine."(in press).

[Publications] 松永俊哉: "持久的運動トレーニングが急性運動負荷による血漿中消化管ホルモンの変動に及ぼす影響"体力研究. 95. 1-7 (1998)

[Publications] 自見厚郎: "ラット膵管結紮膵炎における膵管内投与膵分泌性トリプシンインヒビター(PSTI)の障害阻害効果"膵臓. 13. 25-31 (1998)

[Publications] 船越顕博: "膵炎の器質化、慢性化の病態解明とCamostat経口投与による進展阻止効果の基礎的研究"現代医療. 30. 143-147 (1998)

[Publications] 永松俊哉: "身体運動における負荷強度の違いが膵外分泌作用に及ぼす影響"消化と吸収. 21. 77-80 (1998)

[Publications] 宮坂京子: "図解病態のメカニズム、膵外分泌調節"medicina. 35. 161-165 (1998)

[Publications] 宮坂京子: "CCK受容体"生体の科学 特集受容体. 49. 381-383 (1998)

[Publications] 船越顕博: "CCK-A受容体欠損ラットと摂食行動異常"Frontiers Gastroenterology. 3. 74-83 (1998)

[Publications] 宮坂京子: "加齢と消化吸収"化学と生物. 37. 368-374 (1999)

[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)

[Publications] 船越顕博: "CCK-A受容体遺伝子の構造異常と疾病"消化器科. 28. 598-605 (1999)

[Publications] Funakoshi A.: "Obesity and NIDDM"Shima K.. 248 (1999)

[Publications] Jimi A.: "Oresity and NIDDM"Shima K.. 248 (1999)

[Publications] Kobayashi S.: "Obesity and NIDDM"Shima K.. 248 (1999)

[Publications] 宮坂京子: "サクセスフルエイジング"東京都老人研(ワールドプラニング社). 303 (1998)

[Publications] 宮坂京子(分担): "臨床研修イラストライテッド消火器系マニュアル"羊土社. 197 (1998)

膵外分泌調節におけるCCKと、CCK-A,CCK-B受容体遺伝子発現と機能分担副題:ヒトおよび自然発症CCK-A受容体欠損ラット、遺伝子ターゲティングマウスによる検討

宮坂京子財団法人東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)

[Publications] 宮坂京子: "CCK受容体"生体の科学特集受容体. 49. 381-383 (1998)