HEPAIOCYTE MEMBRANE TRANSPORT MECHANISM OF VARIOUS SUBSTANCES

各种物质的肝细胞膜转运机制

• 批准号: 04454247
• 负责人: YAMAMOTO Toshio
• 金额: $ 3.71万
• 依托单位: SECOND DEPARTMENT OF INTERNAL MEDICINE.KINKI UNIVERSITY SCHOOL OF MEDICINE.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454247/
• 关键词: BILIARY EXCRETION; ATP; ORGANIC ANION; JAUNDICE; HYPERBILIRUBINEMIA; BILE ACIDS; DUBIN-JOHNSON SYNDROME; PRAVASTATIN; ビリルビン; 毛細胆管

(1)Canalicular membrane vesicles (CMV) of hepatocytes were prepared in pure form from the livers of normal SD rats and Eisai hyperbilirubinuric rats (HEBR). Mg^<++> -ATPase and alkaline phosphatase activities were highly enriched in the CMV.[ ^3H]Bilirubin diglucuronide (BDG) was purified from the hile of rats injected with [ ^3H]DELTA ALA.(2)Transport of [ ^3H]BDG and [ ^3H]taurocholate (TC) was observed using CMV from livers of SD rats and EHBR, and any differences of their transport between the 2 rat strains were compared. ATP-dependent [ ^3H]TC transport was present both in SD rat CMV and EHBR CMV.On the other hand, [ ^3H]BDG transport was not ATP-dependent and was increased in the presence of bicarbonate ion. This bicarbonate-dependent [ ^3H]BDG transport was also intact in EHBR CMV.(3)[^<14>C]Pravastatin (PS), One of model organic anions, is excreted in the bile of SD rats. However, its biliary excretion was found to be extremely delayd in EHBR.[^<14>C]PS transport by SD rat CMV was studied and found to be ATP-dependent. In contrast to the in vivo biliary excretion defect of PS, normal ATP-dependent PS transport was found in EHBR CMV.(4)From these results. the postulated defect in ATP-dependent organic anion transport in congenitally jaundiced EHBR was not confirmed and the presence of a novel ATP-dependent organic anion transporter was suugested on the canalicular membrane of rat hepatocytes.

（1）从正常SD大鼠和高胆红素尿大鼠（HEBR）肝脏中制备了肝细胞小管膜囊泡（CMV）。Mg^++> -ATPase和碱性磷酸酶活性在CMV中高度富集。从注射[^3H]DELTA ALA的大鼠脑中纯化[ ^3H]胆红素二葡糖苷酸（BDG）。（2）用SD大鼠和EHBR肝巨细胞病毒（CMV）观察[ ^3H]BDG和[ ^3H]牛磺胆酸（TC）的转运，并比较两种大鼠肝巨细胞病毒（CMV）转运[ ^3H] BDG和[ ^3H] TC的差异。在SD大鼠CMV和EHBR CMV中均存在ATP依赖的[ ^3H]TC转运。另一方面，[ ^3H]BDG转运不依赖于ATP，且在碳酸氢根离子存在时增加。这种碳酸氢盐依赖性[ ^3H]BDG转运在EHBR CMV中也是完整的。(3)[[<14>C]普伐他汀（Pravastatin，PS）是一种模型有机阴离子，经SD大鼠胆汁排泄。然而，它的胆汁排泄被发现在EHBR中极其延迟。研究<14>了SD大鼠CMV的PS转运，发现其具有ATP依赖性。与体内PS的胆汁排泄缺陷相反，在EHBR CMV中发现了正常的ATP依赖性PS转运。（4）从这些结果。在先天性黄疸EHBR中ATP依赖性有机阴离子转运的假定缺陷没有得到证实，而在大鼠肝细胞小管膜上存在一种新的ATP依赖性有机阴离子转运体。

项目成果

足立幸彦,北野元一,小林宏明他: "ビリルビンの輸送、代謝" 胆と膵. 14. 711-716 (1993)

Yukihiko Adachi、Motoichi Kitano、Hiroaki Kobayashi 等：“胆红素的运输和代谢”《胆胰杂志》14. 711-716 (1993)。

奥山佳史,足立幸彦,北野元一他: "HMG-CoA還元酵素阻害剤プラバスタチンのラット肝細胞膜ならびにヒト赤血球膜における輸送機序について" 薬理と治療. 22(Suppl). 13-18 (1993)

Yoshifumi Okuyama、Yukihiko Adachi、Genichi Kitano 等：“HMG-CoA 还原酶抑制剂普伐他汀在大鼠肝细胞膜和人红细胞膜中的转运机制”药理学和治疗 22（增刊）。

ADACHI Y,KOBAYASHI H,SHOUJI M,KITANO M,OKUYAMA Y,AND YAMAMOTO T.: "FUNCTIONAL INTEGRITY OF HEPATOCYTE CANALICULAR MEMBRANE TRANSPORT OF TAUROCHOLATE AND BILIRUBIN DIGLUCURONIDE IN EISAI HYPERBILIRUBINURIA RATS." LIFE SCIENCES. 52. 777-784 (1993)

ADACHI Y、KOBAYASHI H、SHOUJI M、KITANO M、OKUYAMA Y 和 YAMAMOTO T.：“卫材高胆红素尿大鼠肝细胞小管膜转运牛磺胆酸盐和胆红素二葡萄糖苷酸的功能完整性。”

ADACHI Y,KITANO M,KOBAYASHI H,MURATA N,OKUYAMA Y,MIYAWAKI S AND YAMAMOTO T.: "TRANSPORT AND METABOLISM OF" BILIARY TRACT PANCREAS. 14(6). 711-716 (1993)

ADACHI Y、KITANO M、KOBAYASHI H、MURATA N、Okuyama Y、MIYAWAKI S 和 YAMAMOTO T.：“胆道胰腺的运输和代谢”。

MURATA N,ADACHI Y,KAWASAKI N,MIYAWAKI S,ITOH T,KURUMI Y AND YAMAMOTO T.: "COVALENTLY BILIRUBIN-BOUND AMINO ACID OF DELTA-BILIRUBIN.BILIRUBIN." REPORTS OF THE 9TH MEETING OF HEPATIC METABOLISM (ASAHI MEDICAL). p. 39-45 (1993)

MURATA N、ADACHI Y、KAWASAKI N、MIYAWAKI S、ITOH T、KURUMI Y 和 YAMAMOTO T.：“Delta-胆红素的共价胆红素结合氨基酸。胆红素。”