A MODULATORY ROLE OF INTRADUODENAL BILE IN CHOLECYSTOKININ RELEASE IN HUMANS
Intraduodenal bile affects cholecystokinin (CCK) release and pancreatic exocrine secretion in rats, but the effects of intraduodenal bile on CCK release have not yet been well documented in humans. Patients with obstructive jaundice treated with external biliary drainage are a suitable model to dete...
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| Published in | Journal of The Showa Medical Association Vol. 55; no. 4; pp. 319 - 326 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English Japanese |
| Published |
The Showa University Society
1995
昭和大学学士会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0037-4342 2185-0976 |
| DOI | 10.14930/jsma1939.55.319 |
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| Abstract | Intraduodenal bile affects cholecystokinin (CCK) release and pancreatic exocrine secretion in rats, but the effects of intraduodenal bile on CCK release have not yet been well documented in humans. Patients with obstructive jaundice treated with external biliary drainage are a suitable model to determine whether or not CCK release is mediated by bile in humans. Nonspecific interference is observed in radioimmunoassay (RIA) for CCK in plasma. A highly sensitive RIA for the detection of CCK in blood using anti-CCK-8 N-terminus antibody (OAL-656) was developed by extraction of CCK from plasma using a Sep-Pak C18 cartridge. Using this RIA, the modulating role of intraduodenal bile in the regulation of blood CCK release was investigated in ten patients with obstructive jaundice due to cholangioma under management by external biliary drainage (PTCD, ENBD) . Fasting blood CCK levels in the patients after external drainage persisted at a significantly higher level than those in control subjects. Before drainage, administration of a test meal caused a high CCK response, and a high blood CCK concentration was persistently observed. After external drainage, the CCK response to the test meal was significantly lower than before drainage, but the blood CCK concentration was significantly higher compared with control subjects after 20 minutes. These results suggests that intraduodenal bile plays an important modulating role in CCK release in humans. |
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| AbstractList | Intraduodenal bile affects cholecystokinin (CCK) release and pancreatic exocrine secretion in rats, but the effects of intraduodenal bile on CCK release have not yet been well documented in humans. Patients with obstructive jaundice treated with external biliary drainage are a suitable model to determine whether or not CCK release is mediated by bile in humans. Nonspecific interference is observed in radioimmunoassay (RIA) for CCK in plasma. A highly sensitive RIA for the detection of CCK in blood using anti-CCK-8 N-terminus antibody (OAL-656) was developed by extraction of CCK from plasma using a Sep-Pak C18 cartridge. Using this RIA, the modulating role of intraduodenal bile in the regulation of blood CCK release was investigated in ten patients with obstructive jaundice due to cholangioma under management by external biliary drainage (PTCD, ENBD) . Fasting blood CCK levels in the patients after external drainage persisted at a significantly higher level than those in control subjects. Before drainage, administration of a test meal caused a high CCK response, and a high blood CCK concentration was persistently observed. After external drainage, the CCK response to the test meal was significantly lower than before drainage, but the blood CCK concentration was significantly higher compared with control subjects after 20 minutes. These results suggests that intraduodenal bile plays an important modulating role in CCK release in humans. Intraduodenal bile affects cholecystokinin (CCK) release and pancreatic exocrine secretion in rats, but the effects of intraduodenal bile on CCK release have not yet been well documented in humans. Patients with obstructive jaundice treated with external biliary drainage are a suitable model to determine whether or not CCK release is mediated by bile in humans. Nonspecific interference is observed in radioimmunoassay (RIA) for CCK in plasma. A highly sensitive RIA for the detection of CCK in blood using anti-CCK-8 N-terminus antibody (OAL-656) was developed by extraction of CCK from plasma using a Sep-Pak C18 cartridge. Using this RIA, the modulating role of intraduodenal bile in the regulation of blood CCK release was investigated in ten patients with obstructive jaundice due to cholangioma under management by external biliary drainage (PTCD, ENBD) . Fasting blood CCK levels in the patients after external drainage persisted at a significantly higher level than those in control subjects. Before drainage, administration of a test meal caused a high CCK response, and a high blood CCK concentration was persistently observed. After external drainage, the CCK response to the test meal was significantly lower than before drainage, but the blood CCK concentration was significantly higher compared with control subjects after 20 minutes. These results suggests that intraduodenal bile plays an important modulating role in CCK release in humans. ラットでは, 十二指腸内の胆汁の存在がCholecystokinin (CCK) 分泌や膵外分泌に影響を与えることが報告されているが, ヒトにおいて, 胆汁の存在がCCK分泌に及ぼす影響について検討した報告は少ない.閉塞性黄疸における胆汁外瘻症例は, ヒトにおいて胆汁のCCK分泌の制御機構への関与を確認できる最適な病態の一つである.Radioimmunoassay (RIA) 法によるCCK測定では血漿中の非特異的干渉物質の影響が認められ, ラット遊離膵腺房を用いてのアミラーゼ放出によるbioassay法でのCCKの測定では, 胆汁酸によるアミラーゼ放出の増強が指摘され, 閉塞性黄疸症例でのCCK測定に問題を残していた.そこでSep PakC18 Cartridgeを用いてCCKを血漿から抽出することにより, RIA法に影響を及ぼす血漿中の非特異的干渉物質を除去し, CCK-8N端特異抗体OAL-656により, CCKの高感度測定系を開発した.この測定系を用いて, 胆管癌による肝外閉塞性黄疸をきたし, 胆道ドレナージ (PTCD, ENBD) を施行した10症例を対象とし, 胆道ドレナージ前後, 試験食負荷前後の血中CCK濃度を測定し, CCK分泌動態を検討した.胆道ドレナージ後, 空腹時血中CCK濃度は健常人と比較して高値で推移した.試験食負荷による血中CCK濃度の検討では, 胆道ドレナージ前には健常人と比較してCCK分泌の著明な高反応と血中CCK濃度の持続的な上昇を認めた.ドレナージ後には反応性は低下したが, 血中CCK濃度の上昇は健常人と比較して遷延した.以上の結果より, ヒトにおいても十二指腸内の胆汁の存在がCCK分泌に影響を及ぼしていると考えられた. |
| Author | HATTA, Yoshio MITAMURA, Keiji AKITA, Yasushi KURABAYASHI, Mikio TANAKA, Shigeki NIIKAWA, Junichi |
| Author_FL | 秋田 泰 三田村 圭二 八田 善夫 倉林 幹雄 新川 淳一 田中 滋城 |
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| Author_xml | – sequence: 1 fullname: NIIKAWA, Junichi organization: Second Department of Internal Medicine, Showa University School of Medicine – sequence: 1 fullname: MITAMURA, Keiji organization: Second Department of Internal Medicine, Showa University School of Medicine – sequence: 1 fullname: KURABAYASHI, Mikio organization: Second Department of Internal Medicine, Showa University School of Medicine – sequence: 1 fullname: TANAKA, Shigeki organization: Second Department of Internal Medicine, Showa University School of Medicine – sequence: 1 fullname: HATTA, Yoshio organization: Second Department of Internal Medicine, Showa University School of Medicine – sequence: 1 fullname: AKITA, Yasushi organization: Second Department of Internal Medicine, Showa University School of Medicine |
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| References | 8) Takeyama, Y., Nakanishi, H., Ohyanagi, H., et al.: Enhancement of secretagogue-induced phosphoinositide turnover and amylase secretion by bile acids in isolated rat pancreatic acini. J. Gun. Invest. 78: 1604-1611, 1986. 17) Chang, T. M. and Chey, W. Y.: Radioimmunoassay of cholecystokinin. Dig. Dis. Sci . 28: 456-468, 1983. 14) Solomon, T., E.: Regulates of pancreatic secretion. Gun. Gastroenterol. 13: 657-678, 1984. 9) 中西宏之, 大柳治正, 竹山宣典, 他: 急性膵炎における胆汁酸の作用機構. 代謝 24: 727-735, 1987. 23) Lu, L., Louie, D. S., Wider, M., et at.: Extraction and characterization of CCK-releasing peptide mediating feedback regulation of pancreatic secretion. Am. J. Physiol. 256: G430-435, 1989. 21) Iwai, K. and Fushiki, T.: Pancreatic enzyme secretion mediated by nevel peptide : Monitor peptide hypothesis. Pancreas 3: 720-728, 1988. 7) Liddle, R. A., Goldfine, I. D. and Williams, J. A.: Bioassay of plasma cholecysto-kinin in rats : Effects of food, trypsin, inhibitor, and alcohol. Gastroenterology 87: 542-549, 1984. 16) Young. J. D., Lazarus, L. and Chisholm, D. J.: Radioimmunoassay of pancreozymin cholecystokinin in human serum. J. Nucl. Med. 10: 743-745, 1969. 27) 永川宅和, 清水康一, 太田哲生, 他: PTCD後の胆汁分泌能の回復と減黄効果について, 胆と膵3: 1061-1065, 1982. 6) 渡辺伸一郎, 白鳥敬子, 竹内正: CCK Radioimmunoassay の2, 3の問題点. 消化管ホルモンIV, (消化管ホルモン研究会編) , pp. 123-128, 医学図書出版, 東京, 1986. 28) Koide, M., Okabayashi, Y. and Otsuki, M.: Role of endogenous bile on basal and postpra-ndial CCK release in humans. Dig. Dis. Sci. 38: 1284-1290, 1993. 19) Iwai, K., Fukuoka, S., Fushiki, T., et at.: Purification of sequencing of a trypsin sensitive cholecystokinin-releasing peptide from rat pancreatic juice. J. Biol. Chem. 262: 8956-8959, 1987. 20) Fushiki, T, and Iwai, K.: Two hypotheses on the feedback regulation of pancreatic enzyme secretion. FASEB J. 3: 121-126, 1989. 24) Owyang, C., May, D, and Louie, D. S.: Trypsin suppression of pancreatic enzyme secretion. Gastroenterology 91: 637-643, 1986. 29) Khalil, T., Walker, J. P., Wiener, I., et al.: Effect of aging on gallbladder contra. ctions and release of cholecystokinin-33 in humans. Surgery 98: 423-429, 1985. 15) Ihse, I., Lilja, P, and Lundquist, I.: Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion 15: 303-308, 1977. 25) Liener, I. E., Goodale, R. L., Deshmukh, A., et at.: Effect of a trypsin inhibitor from soybeans (Bowman-Birk) on the secretooy activity of the human pancreas. Gastroenterology 94: 419-427, 1988. 22) Miyasaka, K., Guan, D., Liddle, A.. et at.: Feedback regulation by trypsin : Evidence for intraluminal CCK-releasing peptide. Am. J. Physiol. 257: G175-181, 1989. 3) Himeno, S., Tarui, S., Kanayama, S., et at.: Plasma cholecystokinin response after ingestion of liquid meal and intraduodenal infusion of fat, amino acids, or hydrochloric acid in man: Analysis with region specific radio-immunoassay. Am. J. Gastroenterol. 78: 703-707, 1983. 5) Funakoshi, A., Nakano, I., Shinoaaki, H., et al.: High plasma cholecystokinin levels in patients with chronic pancreatitis having abdominal pain. Am. J. Gastroenterol. 81: 1174-1178, 1986. 10) 白鳥敬子, 渡辺伸一郎, 竹内正: 血漿の XA-D-2Resin抽出による CholecystokininのRadioimmunoassay-ヒトにおける食事負荷, 十二指腸内硫酸マグネシウム注入時の血中 Cholecystokininの上昇-. 日消誌 82: 277-287, 1985. 18) Miyasaka, K, and Green, G.: Effect of partial exclusion of pancreatic juice on rat basal pancreatic secretion. Gastroenterology 86: 114-119, 1984. 4) 立石カヨ子, 林長蔵, 姫野誠一, 他: 非交差抗血清を用いたコレシストキニン特異ラジオイムノアッセイの確立. 消化管ホルモンIII, (消化管ホルモン研究会編) , pp. 63-71, 医学図書出版, 東京, 1983. 13) Nakamura, R., Miyasaka, K., Kuyama, Y., et al.: Luminal bile regulates cholecystokinin release in conscious rats. Dig. Dis. Sci. 35: 55-60, 1990. 26) Masclee, A. A. M., Jansen, J. B. M. J., Driessen, W. M. M., et al.: Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients. Dig. Dis. Sci. 34: 353-359, 1989. 12) Green, G. M. and Nasset, E. S.: Importance of bile in regulation of intraluminal proteolytic enzyme activities in the rat. Gastroenterolgy 79: 695-702, 1980. 1) Ivy, A. C. and Oldberg, E.: A hormone mechanism for gallbladder contraction and evacuation. Am. J. Physiol. 65: 599-613, 1928. 11) Nakamura, R., Miyasaka, K., Funakoshi, et al.: Interactions between bile and pancreatic juice diversion on cholecystokinin release and pancreas in conscious rats. Proc. Soc. Exp. Biol. Med. 192: 182-186, 1989. 2) Hashimura, E., Shimizu, F., Nishino, T., et al.: Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross reactive antibody response. J. Immunol. Methods 55: 375-387, 1982 |
| References_xml | – reference: 20) Fushiki, T, and Iwai, K.: Two hypotheses on the feedback regulation of pancreatic enzyme secretion. FASEB J. 3: 121-126, 1989. – reference: 23) Lu, L., Louie, D. S., Wider, M., et at.: Extraction and characterization of CCK-releasing peptide mediating feedback regulation of pancreatic secretion. Am. J. Physiol. 256: G430-435, 1989. – reference: 11) Nakamura, R., Miyasaka, K., Funakoshi, et al.: Interactions between bile and pancreatic juice diversion on cholecystokinin release and pancreas in conscious rats. Proc. Soc. Exp. Biol. Med. 192: 182-186, 1989. – reference: 17) Chang, T. M. and Chey, W. Y.: Radioimmunoassay of cholecystokinin. Dig. Dis. Sci . 28: 456-468, 1983. – reference: 3) Himeno, S., Tarui, S., Kanayama, S., et at.: Plasma cholecystokinin response after ingestion of liquid meal and intraduodenal infusion of fat, amino acids, or hydrochloric acid in man: Analysis with region specific radio-immunoassay. Am. J. Gastroenterol. 78: 703-707, 1983. – reference: 10) 白鳥敬子, 渡辺伸一郎, 竹内正: 血漿の XA-D-2Resin抽出による CholecystokininのRadioimmunoassay-ヒトにおける食事負荷, 十二指腸内硫酸マグネシウム注入時の血中 Cholecystokininの上昇-. 日消誌 82: 277-287, 1985. – reference: 12) Green, G. M. and Nasset, E. S.: Importance of bile in regulation of intraluminal proteolytic enzyme activities in the rat. Gastroenterolgy 79: 695-702, 1980. – reference: 21) Iwai, K. and Fushiki, T.: Pancreatic enzyme secretion mediated by nevel peptide : Monitor peptide hypothesis. Pancreas 3: 720-728, 1988. – reference: 28) Koide, M., Okabayashi, Y. and Otsuki, M.: Role of endogenous bile on basal and postpra-ndial CCK release in humans. Dig. Dis. Sci. 38: 1284-1290, 1993. – reference: 8) Takeyama, Y., Nakanishi, H., Ohyanagi, H., et al.: Enhancement of secretagogue-induced phosphoinositide turnover and amylase secretion by bile acids in isolated rat pancreatic acini. J. Gun. Invest. 78: 1604-1611, 1986. – reference: 29) Khalil, T., Walker, J. P., Wiener, I., et al.: Effect of aging on gallbladder contra. ctions and release of cholecystokinin-33 in humans. Surgery 98: 423-429, 1985. – reference: 18) Miyasaka, K, and Green, G.: Effect of partial exclusion of pancreatic juice on rat basal pancreatic secretion. Gastroenterology 86: 114-119, 1984. – reference: 6) 渡辺伸一郎, 白鳥敬子, 竹内正: CCK Radioimmunoassay の2, 3の問題点. 消化管ホルモンIV, (消化管ホルモン研究会編) , pp. 123-128, 医学図書出版, 東京, 1986. – reference: 16) Young. J. D., Lazarus, L. and Chisholm, D. J.: Radioimmunoassay of pancreozymin cholecystokinin in human serum. J. Nucl. Med. 10: 743-745, 1969. – reference: 24) Owyang, C., May, D, and Louie, D. S.: Trypsin suppression of pancreatic enzyme secretion. Gastroenterology 91: 637-643, 1986. – reference: 25) Liener, I. E., Goodale, R. L., Deshmukh, A., et at.: Effect of a trypsin inhibitor from soybeans (Bowman-Birk) on the secretooy activity of the human pancreas. Gastroenterology 94: 419-427, 1988. – reference: 27) 永川宅和, 清水康一, 太田哲生, 他: PTCD後の胆汁分泌能の回復と減黄効果について, 胆と膵3: 1061-1065, 1982. – reference: 22) Miyasaka, K., Guan, D., Liddle, A.. et at.: Feedback regulation by trypsin : Evidence for intraluminal CCK-releasing peptide. Am. J. Physiol. 257: G175-181, 1989. – reference: 26) Masclee, A. A. M., Jansen, J. B. M. J., Driessen, W. M. M., et al.: Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients. Dig. Dis. Sci. 34: 353-359, 1989. – reference: 4) 立石カヨ子, 林長蔵, 姫野誠一, 他: 非交差抗血清を用いたコレシストキニン特異ラジオイムノアッセイの確立. 消化管ホルモンIII, (消化管ホルモン研究会編) , pp. 63-71, 医学図書出版, 東京, 1983. – reference: 9) 中西宏之, 大柳治正, 竹山宣典, 他: 急性膵炎における胆汁酸の作用機構. 代謝 24: 727-735, 1987. – reference: 14) Solomon, T., E.: Regulates of pancreatic secretion. Gun. Gastroenterol. 13: 657-678, 1984. – reference: 2) Hashimura, E., Shimizu, F., Nishino, T., et al.: Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross reactive antibody response. J. Immunol. Methods 55: 375-387, 1982 – reference: 1) Ivy, A. C. and Oldberg, E.: A hormone mechanism for gallbladder contraction and evacuation. Am. J. Physiol. 65: 599-613, 1928. – reference: 15) Ihse, I., Lilja, P, and Lundquist, I.: Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion 15: 303-308, 1977. – reference: 19) Iwai, K., Fukuoka, S., Fushiki, T., et at.: Purification of sequencing of a trypsin sensitive cholecystokinin-releasing peptide from rat pancreatic juice. J. Biol. Chem. 262: 8956-8959, 1987. – reference: 5) Funakoshi, A., Nakano, I., Shinoaaki, H., et al.: High plasma cholecystokinin levels in patients with chronic pancreatitis having abdominal pain. Am. J. Gastroenterol. 81: 1174-1178, 1986. – reference: 13) Nakamura, R., Miyasaka, K., Kuyama, Y., et al.: Luminal bile regulates cholecystokinin release in conscious rats. Dig. Dis. Sci. 35: 55-60, 1990. – reference: 7) Liddle, R. A., Goldfine, I. D. and Williams, J. A.: Bioassay of plasma cholecysto-kinin in rats : Effects of food, trypsin, inhibitor, and alcohol. Gastroenterology 87: 542-549, 1984. |
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| Title | A MODULATORY ROLE OF INTRADUODENAL BILE IN CHOLECYSTOKININ RELEASE IN HUMANS |
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| ispartofPNX | Journal of The Showa Medical Association, 1995/08/28, Vol.55(4), pp.319-326 |
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