1994 年度実績報告書

コレシストキニン(CCK)とCCKレセプターの遺伝子発現調節、及び膵外分泌調節

研究課題

研究課題/領域番号	06670596
研究機関	(財)東京都老人総合研究所
研究代表者	宮坂京子 (財)東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)
研究分担者	増田正雄 (財)東京都老人総合研究所, 助手 (20260284)
キーワード	コレシストキニン / 膵臓 / レセプター / 遺伝子発現
研究概要	コレシストキニン(CCK)は、消化管ホルモンとして、またneurotransmitter して生体内に広く分布する。しかしその合成と分泌に関する制御機構はおきらかでない部分が多い。本研究の第一の目標は小腸由来のCCK放出因子を精製すること、そのCCK放出因子のCCK分泌に対する作用機序を検討することであるが、まだ結論がでるにはいたっていない。第2には膵由来CCK分泌因子であるPSTIをもちい、遺伝子レベルで、CCKの合成分泌の制御機構との相互関係を検討することである。膵液胆汁外瘻作製のための手術操作により、膵は物理的に障害をうける。PSTI-61は炎症反応物質でもあるので,今回は膵障害の影響を除外するため、鋭敏に膵障害を反映する pancreatitis associated protein(PAP) mRNAの発現が消失する時期を確認してから,実験をおこなった。その結果、膵液胆汁の除外後1,2,4,24時間目の血中CCK,CCKおよびsecretin mRNAはいずれも上昇するが、PSTI-61 mRNAは変動しなかった。つまり、PSTI-61 mRNAの上昇は、膵障害を表すひとつの指標になると考えられた、次に、CCKは迷走神経afferent nerve を興奮させる作用のあることがわかっているので、この点をさらに確認するため、afferent nerveを破壊した(覚醒)ラットを用いて、膵外分泌の変化を検討した。結果はむしろefferent nerveの関与の方がおおきいと言う結果がえられた。Pancreatic PolypeptideやpeptideYYなどは膵腺房細胞にはreceptor が存在しないのにin vivoでは膵外分泌を抑制するが、これらは迷走神経efferent nerveを介して働くことが判明した。さらにCCKのレセプターはA,B2つのサブタイプがクローニングされているので、レセプターの遺伝子発現調節とCCK遺伝子発現調節との相互関係をしらべたところ、現在検討の途中であるが、レセプターのmRNAレベルとCCKmRNAとの間には相互関係はないと思われた。

研究成果
(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Akihiro Funakoshi: "Expression of the cholecystokinin precursor gene in rat tissues." J Gastroenterology. 29. 125-128 (1994)
[文献書誌] Akihiro Funakoshi: "Little or no expression of the cholecystokinin-A receptor gene in the pancreas of diabetic rats(Otsuka Long-Evans Tokushima Fatty-OLETFrats)." Biochem Biophys Res Comm. 199. 482-488 (1994)
[文献書誌] Minoru Ohta: "Effect of long-term exercise under restricted-feeding on intestinal content of cholecystokinin and on the Pancreas in aging rets." Arch Gerontol Geriatr. 18. 43-51 (1994)
[文献書誌] Noburu Kitayama: "Pancreastatin molecular forms in normal human plasma." Life Sci. 54. 975-981 (1994)
[文献書誌] Akihiro Funakoshi: "Effect of a new CCK antagonist(FK480)on gene expressions of cholecystokinin and secretin in rat intestine." J Gastroenterology. 29. 385-387 (1994)
[文献書誌] Hiroshi Tomita: "Lack of effect of cholecystokinin receptor antagonist(CR1505)on recovery of experimental pancreatitis after pancreatic duct occlusion in rats." Pancreas. 9. 638-645 (1994)
[文献書誌] Hiroshi Tomita: "Direct,concentration-dependent inhibition by taurocholate of pancreatic exocrine secretion and CCK release in conscious rats." Dig Dis Sci. 39. 1544-1549 (1994)
[文献書誌] Kyoko Miyasaka: "Time course of recovery from pancreatic hypertrophy during partial exclusion of bile pancreatic juice." Jpn J physiol. 44. 243-354 (1994)
[文献書誌] Kenji Okubo: "Mechanisms of stimulatory effect of neuromedin C on pancreatic exocrine secretion in conscious rats." Pancreas. 9. 585-590 (1994)
[文献書誌] Kenji Okubo: "Secretory capacity of pancreatic protein during luminal feedback regulation in conscious rats." Jpn J Physiol. 44. 205-219 (1994)
[文献書誌] Kyoko Miyasaka: "Lack of satiety effect of cholecystokinin(CCK)in a new rat model not expressing the CCK-A receptor gene." Neurosci Lett. 180. 143-146 (1994)
[文献書誌] Masao Masuda: "Vagal efferent nerve-dependent inhibitory action of pancreatic polypeptide and peptide YY in conscious rats: comparison with somatostatin." J Autonomic Nervous System. 50. 131-138 (1994)
[文献書誌] Kyoko Miyasaka: "lnvolvement of gene expressions of cholecystokinin and secretin in luminal feedback regulation in conscious rats." Pancreas. 10. 200-203 (1994)
[文献書誌] Akihiro Funakoshi: "Effect of a CCK antagonist(CR-1505)on gene expressions of cholecystokinin and secretin in rat intestine." Pancreas. 10. 118-122 (1994)
[文献書誌] Hitotsugu Shinozaki: "Stimualtory effect of ursodeoxycholate(UDCA)on pancreatic exocrine secretion in in vitro study." Pancreas. (in press).
[文献書誌] Akihiro Funakoshi: "The effect of cholecystokinin(CCK)angatonist(CR-1505)on gene expressions of CCK and secretin in rat intestine." Biomed Res.(in press).
[文献書誌] Akihiro Funakoshi: "The effect of cholecystokinin(CCK)angatonist(CR-1505)on gene expressions of CCK and secretin in rat intestine." Biomed Res.(in press). Hirotsugu Shinozaki:
[文献書誌] "Stimulatory effect of CCK -JMV-180,an analog of cholecystokinin on pancreas" Biomed Res. (in press).
[文献書誌] Kyoko Miyasaka: "Bilateral vagotomy abolished inhibitory effect of PP and PYY on pancreatic exocrine secretion in conscious rats." Bimed Res. (in press).
[文献書誌] Masahiro Matsumoto: "Early detection of pancreatic exocrine insufficincy in Otsuka Long-Evans Tokushima Fattty(OLETF)rats." BiomedRes.(in press).
[文献書誌] Kyoko Miyasaka: "Regulation of gene expressions of pancreatic secretory trypsin inhibitor-61 and -56by bile and pancreatic juice in rats." Pancreas. (in press).
[文献書誌] Akihiro Funakoshi: "Changes in gene expressions of pancreatitis associated protein and pancreatic secretory trypsin inhibitors in expcrimcntal pancrcatitis produccd by pancrcatic duct occlusion in rats.Comparison with gen eexpressions of cholecystokinin and secretin." Pancreas. (in press).
[文献書誌] Masao Masuda: "Cholincrgic stimulatory effect of intragastric administratrion of a prostaglandin E2 analgue on pancreatic exocrine secretion in conscious rats." Pancreas. (in press).
[文献書誌] Naoko Sazaki: "Effects of intraduodenal administration of alow dose of cholecystokinin(CCK)antagonist(CR-1505)on the plasma and intestinal CCK concentrations,and the level of CCK mRNA." J Gastroenterol. (in press).
[文献書誌] Kenii Okubo: "Stimulatory effect of PACAP on pancreatic exocrine secretion in vivo in conscious rats." Biomed Res.
[文献書誌] 富田浩: "覚醒ラットにおける両側迷走神経切離のcholecystokinin分泌と膵外分泌に対する影響。" 日本消化器病学会雑誌. 91. 287-292 (1994)
[文献書誌] 富田浩: "ラット膵管結紮膵炎の発症、進展、回復におよぼすセルレイン過剰投与の影響" 膵臓. 9. 278-283 (1994)
[文献書誌] 増田正雄: "覚醒ラットにおけるプロスタグランジンE_2誘導体の膵外分泌に対する作用" 臨床と研究. 71. 243-244 (1994)
[文献書誌] 太田稔: "肝細胞癌患者において肝動脈塞栓術(TAE)施行後のヒト肝細胞増殖因子(hHGF)とアポリポ蛋白A-IVfの血中濃度変化" 臨床と研究. 71. 2197-2199 (1994)
[文献書誌] 船越顕博: "ウルソデオキシコール酸(UDCA)のラット小腸CCK,セクレチン遺伝子発現に対する作用" 日本消化器病学会雑誌. 91. 1469-速報 (1994)
[文献書誌] 自見厚郎: "Otsuka Long-Eyans Tokushima Fatty (OLETF)ラットにおける膵組織変化-ラ氏島と腺房" Peptide Hormone in Pancreas. 14. 15-19 (1994)
[文献書誌] 船越顕博: "CCK拮抗剤の十二指腸内CCK,secretin遺伝子発現に及ぼす影響" Progress in Medicine. 14. 97-100 (1994)
[文献書誌] 宮坂京子: "中心静脈栄養施行時の小腸粘膜内CCK,secretinの遺伝子発現と小腸粘膜像" 消化と吸収. 17. 77-79 (1994)

1994 年度 実績報告書

コレシストキニン(CCK)とCCKレセプターの遺伝子発現調節、及び膵外分泌調節

研究代表者

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

研究成果

[文献書誌] Akihiro Funakoshi: "Expression of the cholecystokinin precursor gene in rat tissues." J Gastroenterology. 29. 125-128 (1994)

[文献書誌] Akihiro Funakoshi: "Little or no expression of the cholecystokinin-A receptor gene in the pancreas of diabetic rats(Otsuka Long-Evans Tokushima Fatty-OLETFrats)." Biochem Biophys Res Comm. 199. 482-488 (1994)

[文献書誌] Minoru Ohta: "Effect of long-term exercise under restricted-feeding on intestinal content of cholecystokinin and on the Pancreas in aging rets." Arch Gerontol Geriatr. 18. 43-51 (1994)

[文献書誌] Noburu Kitayama: "Pancreastatin molecular forms in normal human plasma." Life Sci. 54. 975-981 (1994)

[文献書誌] Akihiro Funakoshi: "Effect of a new CCK antagonist(FK480)on gene expressions of cholecystokinin and secretin in rat intestine." J Gastroenterology. 29. 385-387 (1994)

[文献書誌] Hiroshi Tomita: "Lack of effect of cholecystokinin receptor antagonist(CR1505)on recovery of experimental pancreatitis after pancreatic duct occlusion in rats." Pancreas. 9. 638-645 (1994)

[文献書誌] Hiroshi Tomita: "Direct,concentration-dependent inhibition by taurocholate of pancreatic exocrine secretion and CCK release in conscious rats." Dig Dis Sci. 39. 1544-1549 (1994)

[文献書誌] Kyoko Miyasaka: "Time course of recovery from pancreatic hypertrophy during partial exclusion of bile pancreatic juice." Jpn J physiol. 44. 243-354 (1994)

[文献書誌] Kenji Okubo: "Mechanisms of stimulatory effect of neuromedin C on pancreatic exocrine secretion in conscious rats." Pancreas. 9. 585-590 (1994)

[文献書誌] Kenji Okubo: "Secretory capacity of pancreatic protein during luminal feedback regulation in conscious rats." Jpn J Physiol. 44. 205-219 (1994)

[文献書誌] Kyoko Miyasaka: "Lack of satiety effect of cholecystokinin(CCK)in a new rat model not expressing the CCK-A receptor gene." Neurosci Lett. 180. 143-146 (1994)

[文献書誌] Masao Masuda: "Vagal efferent nerve-dependent inhibitory action of pancreatic polypeptide and peptide YY in conscious rats: comparison with somatostatin." J Autonomic Nervous System. 50. 131-138 (1994)

[文献書誌] Kyoko Miyasaka: "lnvolvement of gene expressions of cholecystokinin and secretin in luminal feedback regulation in conscious rats." Pancreas. 10. 200-203 (1994)

[文献書誌] Akihiro Funakoshi: "Effect of a CCK antagonist(CR-1505)on gene expressions of cholecystokinin and secretin in rat intestine." Pancreas. 10. 118-122 (1994)

[文献書誌] Hitotsugu Shinozaki: "Stimualtory effect of ursodeoxycholate(UDCA)on pancreatic exocrine secretion in in vitro study." Pancreas. (in press).

[文献書誌] Akihiro Funakoshi: "The effect of cholecystokinin(CCK)angatonist(CR-1505)on gene expressions of CCK and secretin in rat intestine." Biomed Res.(in press).

[文献書誌] Akihiro Funakoshi: "The effect of cholecystokinin(CCK)angatonist(CR-1505)on gene expressions of CCK and secretin in rat intestine." Biomed Res.(in press). Hirotsugu Shinozaki:

[文献書誌] "Stimulatory effect of CCK -JMV-180,an analog of cholecystokinin on pancreas" Biomed Res. (in press).

[文献書誌] Kyoko Miyasaka: "Bilateral vagotomy abolished inhibitory effect of PP and PYY on pancreatic exocrine secretion in conscious rats." Bimed Res. (in press).

[文献書誌] Masahiro Matsumoto: "Early detection of pancreatic exocrine insufficincy in Otsuka Long-Evans Tokushima Fattty(OLETF)rats." BiomedRes.(in press).

[文献書誌] Kyoko Miyasaka: "Regulation of gene expressions of pancreatic secretory trypsin inhibitor-61 and -56by bile and pancreatic juice in rats." Pancreas. (in press).

[文献書誌] Masao Masuda: "Cholincrgic stimulatory effect of intragastric administratrion of a prostaglandin E2 analgue on pancreatic exocrine secretion in conscious rats." Pancreas. (in press).

[文献書誌] Naoko Sazaki: "Effects of intraduodenal administration of alow dose of cholecystokinin(CCK)antagonist(CR-1505)on the plasma and intestinal CCK concentrations,and the level of CCK mRNA." J Gastroenterol. (in press).

[文献書誌] Kenii Okubo: "Stimulatory effect of PACAP on pancreatic exocrine secretion in vivo in conscious rats." Biomed Res.

[文献書誌] 富田浩: "覚醒ラットにおける両側迷走神経切離のcholecystokinin分泌と膵外分泌に対する影響。" 日本消化器病学会雑誌. 91. 287-292 (1994)

[文献書誌] 富田浩: "ラット膵管結紮膵炎の発症、進展、回復におよぼすセルレイン過剰投与の影響" 膵臓. 9. 278-283 (1994)

[文献書誌] 増田正雄: "覚醒ラットにおけるプロスタグランジンE_2誘導体の膵外分泌に対する作用" 臨床と研究. 71. 243-244 (1994)

[文献書誌] 太田稔: "肝細胞癌患者において肝動脈塞栓術(TAE)施行後のヒト肝細胞増殖因子(hHGF)とアポリポ蛋白A-IVfの血中濃度変化" 臨床と研究. 71. 2197-2199 (1994)

[文献書誌] 船越顕博: "ウルソデオキシコール酸(UDCA)のラット小腸CCK,セクレチン遺伝子発現に対する作用" 日本消化器病学会雑誌. 91. 1469-速報 (1994)

[文献書誌] 自見厚郎: "Otsuka Long-Eyans Tokushima Fatty (OLETF)ラットにおける膵組織変化-ラ氏島と腺房" Peptide Hormone in Pancreas. 14. 15-19 (1994)

[文献書誌] 船越顕博: "CCK拮抗剤の十二指腸内CCK,secretin遺伝子発現に及ぼす影響" Progress in Medicine. 14. 97-100 (1994)

[文献書誌] 宮坂京子: "中心静脈栄養施行時の小腸粘膜内CCK,secretinの遺伝子発現と小腸粘膜像" 消化と吸収. 17. 77-79 (1994)

1994 年度実績報告書

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