DRUG EXCRETION MEDIATED BY A NEW PROTOTYPE OF POLYSPECIFIC TRANSPORTER
DRUG EXCRETION MEDIATED BY A NEW PROTOTYPE OF POLYSPECIFIC TRANSPORTER
复制标题
DOI：
10.1038/372549a0
复制
发表时间：
1994-12-08
期刊：
影响因子：
64.8
通讯作者：
KOEPSELL, H
中科院分区：
文献类型：
--
作者：
GRUNDEMANN, D;GORBOULEV, V;KOEPSELL, H
不同类型和结构的阳离子药物（例如抗组胺药、抗心律失常药、镇静剂、阿片类药物、细胞抑制剂和抗生素）在哺乳动物中通过肾近端小管上皮细胞和肝脏中的肝细胞排泄（1-4）。在近端小管中，涉及两个功能完全不同的运输系统，它们位于基底外侧和管腔质膜上，与先前确定的神经元单胺转运蛋白和atp依赖的多药物输出蛋白不同（1-3,5-12）。在这里，我们报道了从大鼠肾脏中分离出的一种互补DNA，该DNA编码556个氨基酸的膜蛋白OCT1，该蛋白具有在肾近端小管基底外膜上摄取有机阳离子和将有机阳离子摄取到肝细胞的功能特征。OCT1与任何其他已知的蛋白质都不同源，它存在于肾脏、肝脏和肠道中。由于OCT1转运不同结构的疏水和亲水有机阳离子，因此被认为是一种新的多特异性转运体原型，对药物消除具有重要意义。
CATIONIC drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver(1-4). In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and ATP-dependent multidrug exporting proteins(1-3,5-12). Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCT1 is not homologous to any other known protein and is found in kidney, liver and intestine. As OCT1 translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prototype of polyspecific transporters that are important for drug elimination.