...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney
【24h】

Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney

机译：地高辛转运蛋白及其在大鼠肾脏中表达的同系物的分离与鉴定

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K-m = 7.8 muM and ouabain, K-m = 0.38 muM), thyroid hormone (triiodothyronine, K. = 5.9 muM and thyroxine), cAMP, and methotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (Km = 8.0 muM) and triioclothyronine (Km = 1.9 muM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP40/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney. [References: 40]
机译：地高辛是治疗心力衰竭的最常用处方药之一，主要通过肾脏从循环系统中清除。 P-糖蛋白被很好地表征为肾单位顶膜上的地高辛泵。但是，关于基底外侧膜的转运机制知之甚少。我们从人肾脏中分离了一种有机阴离子转运蛋白（OATP4C1）。人OATP4C1是在人肾脏中表达的有机阴离子转运多肽（OATP）家族的第一个成员。分离的cDNA编码具有12个跨膜结构域的724aa的多肽。基因组组织由位于染色体5q21上的13个外显子组成。它的大鼠对应物Oatp4c1也从大鼠肾脏中分离出来。人OATP4C1以钠不依赖的方式转运强心苷（地高辛，K-m = 7.8μM和哇巴因，K-m = 0.38μM），甲状腺激素（三碘甲状腺素，K。= 5.9μM和甲状腺素），cAMP和氨甲蝶呤。大鼠Oatp4c1还转运地高辛（Km = 8.0μM）和三碘布罗宁（Km = 1.9μM）。免疫组织化学分析表明，大鼠Oatp4c1蛋白位于肾脏近端小管细胞的基底外侧膜中。这些数据表明，人OATP40 /大鼠Oatp4c1可能是地高辛和各种化合物进入肾脏尿液的运输途径的第一步。 [参考：40]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号