| Project/Area Number |
06454268
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kinki University, Second Department of Internal Miedicine. |
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Principal Investigator |
ADACHI Yukihiko Kinki University School of Medicine, Second Department of Internal Medicine, Associate Professor., 医学部, 助教授 (50111026)
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| Co-Investigator(Kenkyū-buntansha) |
NANNO Tatsuo Kinki University, School of Medicine, Second Department of Internal Medicine, As, 医学部, 助教授 (40189220)
YAMAMOTO Toshio Kinki University, Life Science Institute, Professor., ライフサイエンス研究所, 教授 (50088522)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | organic anion / bilirubin / pravastatin / taurocholate / UDP-glucuronosyltransferase / biliary excretion / Gilbert's syndrome / Rotor's syndrome / 肝細胞内輸送 / 胆汁中排泄 / グルクロン酸抱合 / 閉塞性黄疸 |
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| Research Abstract |
To elucidate hepatocyte transport and metabolism of organic ions and its relevance to clinical medicine, the following studies were perfomed. (1) Uptake of pravastatin, an organic anion excreted into bile, by hepatocyte canalicular membrane vesicles (CMV) from normal and congenitally jaundiced Eisai hyperbilirubinuria rats (EHBR) was studied. Pravastatin uptake was stimulated in the co-presence of ATP and transmembrane upward pH gradient. This transport was absent in EHBR.These results indicate that this transport system may physiologically transport organic anions through canalicular membrane.
(2) Bile canalicles were ligated (BDL) and uptakes of radiolabeled taurocholate and pravastatin were observed. Both of the transports decreased markedly 2 days after BDL.This will give pathophysiological basis for reduced bile flow after release of obstrucrive jaundice in clinical medicine. (3) Gilbert's and Type II Crigler-Najjar syndromes are characterized by the decrease in te hepatic microsomal bilirubin UDP-glucuronosyltransferase (BUGT ; UGT 1^<**>1) to 30 and 10 % of the normal activity, respectively. The genes for BUGT was analyzed mainly in Gilbert's syndrome, and heterozygous mis-sense mutations were found in the coding region or homozygous TATA box mutation (presence of additional TA) was found in the promoter region in the most of the cases. These results indicate that Gilbert's syndrome is inherited both as a dominant and a recessive trait.
(4) In the liver of patients with Rotor's syndrome, we found no immunohistochemical staining of glutathione S-transferase (GST), indicating the absence of whole GST isozymes in the hepatocytes. (5) The above results were discussed refering to the litratures on the metabolism and transport of bilirubin and other organic anions.
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