Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
AAPS J. 2013 Apr;15(2):581-8. doi: 10.1208/s12248-013-9465-7. Epub 2013 Feb 22.
In the kidney, human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are the major transporters for the secretion of cationic drugs into the urine. In the human kidney, OCT2 mediates the uptake of drugs from the blood at the basolateral membrane of tubular epithelial cells, and MATE1 and MATE2-K secrete drugs from cells into the lumen of proximal tubules. However, the expression of these transporters depends on the species of the animal. In the rodent kidney, OCT1 and OCT2 are expressed at the basolateral membrane, and MATE1 localizes at the brush-border membrane. Together, these transporters recognize various compounds and have overlapping, but somewhat different, substrate specificities. OCTs and MATEs can transport important drugs, such as metformin and cisplatin. Therefore, functional variation in OCTs and MATEs, including genetic polymorphisms or inter-individual variation, may seriously affect the pharmacokinetics and/or pharmacodynamics of cationic drugs. In this review, we summarize the recent findings and clinical importance of these transporters.
在肾脏中，有机阳离子转运体（OCTs）和多药和毒素外排蛋白（MATEs）是将阳离子药物分泌到尿液中的主要转运体。在人肾脏中，OCT2 介导药物从血液中摄取到肾小管上皮细胞的基底外侧膜，而 MATE1 和 MATE2-K 将药物从细胞分泌到近曲小管腔中。然而，这些转运体的表达取决于动物的种类。在啮齿动物肾脏中，OCT1 和 OCT2 表达在基底外侧膜上，而 MATE1 定位于刷状缘膜上。这些转运体共同识别各种化合物，具有重叠但略有不同的底物特异性。OCTs 和 MATEs 可以转运重要的药物，如二甲双胍和顺铂。因此，OCTs 和 MATEs 的功能变异，包括遗传多态性或个体间差异，可能会严重影响阳离子药物的药代动力学和/或药效学。在这篇综述中，我们总结了这些转运体的最新发现和临床意义。
