Transport of drugs in the kidney by the human organic cation transporter, OCT2 and its genetic variants

被引:92
作者
Fujita, T [1 ]
Urban, TJ [1 ]
Leabman, MK [1 ]
Fujita, K [1 ]
Giacomini, KM [1 ]
机构
[1] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
关键词
organic cation transporter; pharmacokinetics; kidney transporters; metformin; pharmacogenetics;
D O I
10.1002/jps.20536
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The human organic cation transporter 2 (OCT2, SLC22A2) is a multispecific transporter of organic cations, including many clinically used drugs. OCT2 is primarily responsible for the uptake of organic cations across the basolateral membrane of renal tubular epithelial cells and is considered a major transporter in the active secretion of organic cations in the kidney. Uptake of organic cations by OCT2 is driven by the inside-negative membrane potential and is pH-sensitive. Regulation of OCT2 at the transcriptional level by steroid hormones and at the protein level by various protein kinases has been described. Several human genetic variants in the coding region of OCT2 have been identified and functionally characterized, including both polymorphic and rare variants. A variety of structurally diverse compounds have been shown to interact with OCT2, including endogenous compounds, drugs, and dietary supplements. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:25 / 36
页数:12
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