Structure and Function of Drug Transporters in the Intestinal and Renal Epithelial Cells

肠和肾上皮细胞中药物转运蛋白的结构和功能

基本信息

批准号：
02807200
负责人：
INUI Ken-ichi
金额：
$ 1.02万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807200/
关键词：
Intestinal Epithelial Cell Renal Epithelial Cell Cultured Epithelial Cell Transporter Transcellular Transport Organic Cation Dipeptide Proton-Coupled Transport 刷子縁膜吸収・分泌

项目摘要

We have studied the cellular and molecular mechanisms of the drug transporters such as H^+/organic cation antiporter (secretion) in the renal brush-border membranes and H^+/dipeptide cotransporter (absorption) in the intestinal brush-border membranes.1) Substrate Specificity of the H^+/Organic Cation Antiporter and H^+/Dipeptide Cotransporter : Anticancer agent bestatin, a dipeptide containing an unusual amino acid, was transported via the H^+/dipeptide cotransporter in the intestinal brushborder membranes, and via the H^+/organic cation antiporter and the H^+/dipeptide cotransporter in the renal brush-border membranes.2) Transcellular Transport of Organic Cation across Monolayers of Kidney Epithelial Cell Line LLC-PK_1 : Tetraethylammonium (TEA) was taken up progressively by the cell monolayers from the basolateral side, and was transported unidirectionally to the apical side. The basolateral-to-apical transport of TEA was stimulated by lowering pH of the apical side. The TEA efflux from the cell monolayers to the apical side caused a decrease in the intracellular pH.3)Transcellular Transport -of Oral Cephalosporins and Bestatin by Monolayers of Human Intestinal Epithelial Cell Line Caco-2 : Oral cephalosporins accumulated in the Caco-2 cell monolayers via the H^+/dipeptide cotransporter localized in the apical membranes and that a specific transport system was involved in the efflux of these antibiotics across the basolateral membranes.4)Expression of Dipeptide Transporters in Xenopus Oocytes : The expression of H^+-dependent dipeptide transporters was observed in Xenopus laevis oocytes injected with poly (A)^+mRNA from Caco-2 cells.

我们已经研究了药物转运蛋白的细胞和分子机制，例如肾刷膜膜中的h^+/有机阳离子抗抗突（分泌）和H^+/二肽共转移蛋白（吸收）（吸收）。：抗癌剂Bestatin是一种含有异常氨基酸的二肽，通过H^+/二肽共转移蛋白在肠道灌木膜中运输，并通过H^+/有机阳离子抗腐蚀剂和H^+/Dippthe Cotransporter在肾脏中的H^+/Dippthe Cotransers.2）替代了纤维素。2）肾上皮细胞系LLC-PK_1：四乙基铵（TEA）被基底外侧的细胞单层逐渐吸收，并将其单向运输到顶端。通过降低顶端的pH，刺激了茶的基底外侧到茶的运输。从细胞单层到顶端的茶水外流导致细胞内PH.3）跨细胞运输 - 口腔头孢菌素和bestatin的人类肠上皮细胞系CACO-2：口腔中性头孢菌素的单层通过caco-2细胞单层积累的apiale aptor caco-embrowan in Aptor Caco-2：Optial caco-2： 4）在Xenopus卵母细胞中的二肽转运蛋白的表达：H^+依赖性二肽转运蛋白的表达在Xenopus laevis laevis laevis oocytes中观察到h^+依赖性二肽转运蛋白的表达。