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A study on the vesicular transport of canalicular transporters

微管转运蛋白的囊泡转运研究

基本信息

批准号：
16590634
负责人：
TAKIKAWA Hajime
金额：
$ 2.11万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590634/
关键词：
bile acid organic anion organic cation transporter vesicular transport biliary excretion colchicine Bsep BSP ICG エリスロマイシン胆汁中排泄胆汁流量 bile salt export pump(Bsep)

项目摘要

Colchicine, an inhibitor of the intracellular vesicular transport, has been reported to inhibit the biliary excretion of bile acids and organic anions, but the previous findings are controversial.In order to systematically evaluate the effect of colchicine on the biliary excretion of cholephilic compounds, we studied the effect of colchicines on the biliary excretion of substrates of various canalicular transporters. Substrates of various canalicular transporters were infused at the rate of or above their excretory maximum into rats, and the effect of colchicine on their biliary excretion was studied. The biliary excretion of taurocholate was markedly inhibited by colchicine, whereas that of tauroursodeoxycholate was not inhibited.The biliary excretory maximum of taurolithocholate-sulfate and sulfobromophthalein, substrates of mrp2, that of erythromycin, a substrate of P-gp were not affected by colchicine.The different excretory maximum of taurocholate and tauroursodeoxycholate and the different effect of colchicine on the excretion of these bile acids are considered to be different regulatory mechanisms of vesicular targeting of the Bsep to the canalicular membrane by these bile acid conjugates. The vesicular targeting of Mrp2 and the P-gp to the canalicular membrane is considered to be colchicine insensitive in the absence of bile acid coadministration.

秋水仙碱是细胞内囊泡运输的抑制剂，有报道称可抑制胆汁酸和有机阴离子的胆道排泄，但以往的研究结果存在争议。为了系统地评价秋水仙碱对胆亲胆化合物排泄的影响，我们研究了秋水仙碱对各种小管转运体底物胆排泄的影响。以不同小管转运体的最大排泄速率或高于排泄速率的底物输注大鼠，研究秋水仙碱对大鼠胆道排泄的影响。秋水仙碱对牛磺胆酸胆酸胆的分泌有明显抑制作用，而对牛磺酸去氧胆酸胆酸胆酸胆的分泌没有抑制作用。秋水仙碱不影响mrp2底物硫酸牛磺酸胆碱和磺溴眼啡的胆排泄量最大值，也不影响P-gp底物红霉素的胆排泄量最大值。牛磺酸胆酸盐和牛磺酸去氧胆酸盐的不同排泄最大值以及秋水仙碱对这些胆汁酸排泄的不同影响被认为是这些胆汁酸偶联物将Bsep囊泡靶向到小管膜的不同调节机制。在没有胆汁酸共给药的情况下，Mrp2和P-gp对小管膜的囊泡靶向被认为是秋水仙碱不敏感的。

项目成果

期刊论文数量（40）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biliary excretion of olmesartan, an anigotensin II receptor antagonist, in the rat

DOI：
10.1111/j.1440-1746.2005.03792.x
发表时间：
2005-05
期刊：
Journal of Gastroenterology and Hepatology
影响因子：
4.1
作者：
Motoe Takayanagi;N. Sano;H. Takikawa
通讯作者：
Motoe Takayanagi;N. Sano;H. Takikawa

Biliary excretion of taurocholate, organic anions and vinblastine in rats with α-naphthylisothiocyanate-induced cholestasis

DOI：
10.1111/j.1440-1746.2005.03794.x
发表时间：
2005-07-01
期刊：
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
影响因子：
4.1
作者：
Kurihara, H;Sano, N;Takikawa, H
通讯作者：
Takikawa, H

Effect of cyclosporin A on the biliary excretion of cholephilic compounds in rats.

DOI：
10.1016/j.hepres.2005.08.013
发表时间：
2006-03
期刊：
Hepatology research : the official journal of the Japan Society of Hepatology
影响因子：
0
作者：
Masahiro Akashi;A. Tanaka;H. Takikawa
通讯作者：
Masahiro Akashi;A. Tanaka;H. Takikawa

Comparison of urinary excretion of pravastatin and temocapril in bile duct-ligated rats and Eisai hyperbilirubinemic rats

胆管结扎大鼠和卫材高胆红素血症大鼠尿中普伐他汀和替莫普利的排泄比较