Organic cation transporter OCT/SLC22A and H+/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents
Organic cation transporter OCT/SLC22A and H+/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents
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DOI：
10.1016/j.bcp.2010.11.016
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发表时间：
2011-03-01
影响因子：
5.8
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
--
作者：
Yonezawa, Atsushi;Inui, Ken-ichi
铂类药物长期以来被广泛应用于肿瘤化疗。顺铂、卡铂、奥沙利铂和奈达铂具有由铂、载体基团和离去基团组成的共同化学结构，并且经历类似的细胞毒性机制。然而，每种药物的疗效和不良反应不同，尽管所涉及的分子机制尚不清楚。近年来，研究发现有机阳离子转运蛋白OCT/SLC 22 A、多药和毒素排出MATE/SLC 47 A在铂类药物的药代动力学中发挥作用。仅顺铂诱导肾毒性，并且毒性是肾脏特异性的。肾脏特异性OCT 2介导顺铂的转运，是顺铂诱导的肾毒性的决定因素。此外，顺铂和奥沙利铂是这些转运蛋白的底物，但卡铂和奈达铂不是。底物特异性可以调节铂类药物的性质。在本文中，我们将讨论OCT和MATE的特点，并展示了最近的话题之间的关系，铂剂的有机阳离子转运蛋白的运输和他们的药理学特性。(C)2010年爱思唯尔公司All rights reserved.
Platinum agents have been widely used in cancer chemotherapy for a long time. Cisplatin, carboplatin, oxaliplatin and nedaplatin have a common chemical structure consisting of platinum, carrier groups and leaving groups, and undergo the similar mechanism of cytotoxicity. However, each agent differs in its efficacy and adverse effects, although the molecular mechanism involved is unclear. Recently, it was reported that organic cation transporter OCT/SLC22A, and multidrug and toxin extrusion MATE/SLC47A play a role in the pharmacokinetics of platinum agents. Only cisplatin induces nephrotoxicity and the toxicity is kidney-specific. Kidney-specific OCT2 mediates the transport of cisplatin and is the determinant of cisplatin-induced nephrotoxicity. In addition, cisplatin and oxaliplatin are substrates for these transporters, but carboplatin and nedaplatin are not. Substrate specificity could regulate the features of platinum agents. In this commentary, we will discuss the characteristics of OCT and MATE, and demonstrate the recent topics about the relationship between the transport of platinum agents by organic cation transporters and their pharmacological characteristics. (C) 2010 Elsevier Inc. All rights reserved.