The organic cation transporters (OCTs) OCT1, OCT2, OCT3, novel OCT (OCTN)1, OCTN2, multidrug and toxin exclusion (MATE)1, and MATE kidney-specific 2 are polyspecific transporters exhibiting broadly overlapping substrate selectivities. They transport organic cations, zwitterions, and some uncharged compounds and operate as facilitated diffusion systems and/or antiporters. OCTs are critically involved in intestinal absorption, hepatic uptake, and renal excretion of hydrophilic drugs. They modulate the distribution of endogenous compounds such as thiamine, L-carnitine, and neurotransmitters. Sites of expression and functions of OCTs have important impact on energy metabolism, pharmacokinetics, and toxicity of drugs, and on drug-drug interactions. In this work, an overview about the human OCTs is presented. Functional properties of human OCTs, including identified substrates and inhibitors of the individual transporters, are described. Sites of expression are compiled, and data on regulation of OCTs are presented. In addition, genetic variations of OCTs are listed, and data on their impact on transport, drug treatment, and diseases are reported. Moreover, recent data are summarized that indicate complex drug-drug interaction at OCTs, such as allosteric high-affinity inhibition of transport and substrate dependence of inhibitor efficacies. A hypothesis about the molecular mechanism of polyspecific substrate recognition by OCTs is presented that is based on functional studies and mutagenesis experiments in OCT1 and OCT2. This hypothesis provides a framework to imagine how observed complex drug-drug interactions at OCTs arise. Finally, preclinical in vitro tests that are performed by pharmaceutical companies to identify interaction of novel drugs with OCTs are discussed. Optimized experimental procedures are proposed that allow a gapless detection of inhibitory and transported drugs.

中文翻译：

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健康和疾病中的有机阳离子转运蛋白。

有机阳离子转运蛋白（OCT）OCT1，OCT2，OCT3，新型OCT（OCTN）1，OCTN2，多种药物和毒素排除（MATE）1和MATE肾脏特异性2是多特异性转运蛋白，具有广泛的底物选择性重叠。它们运输有机阳离子，两性离子和一些不带电荷的化合物，并作为促进扩散的系统和/或反向转运体起作用。OCT关键参与亲水性药物的肠道吸收，肝吸收和肾脏排泄。它们调节内源性化合物（如硫胺素，左旋肉碱和神经递质）的分布。OCT的表达和功能位点对能量代谢，药物动力学和药物毒性以及药物与药物的相互作用具有重要影响。在这项工作中，将介绍有关人类OCT的概述。人类OCT的功能特性 描述了包括确定的底物和单个转运蛋白的抑制剂。汇编表达位点，并提供有关OCT调节的数据。此外，还列出了OCT的遗传变异，并报告了其对运输，药物治疗和疾病的影响数据。此外，最近的数据总结表明在OCT上复杂的药物相互作用，例如对变构的高亲和力抑制转运和底物对抑制剂功效的依赖性。基于OCT1和OCT2的功能研究和诱变实验，提出了关于OCTs识别多特异性底物分子机制的假说。该假设提供了一个框架，可以想象在OCT处如何观察到复杂的药物相互作用。最后，讨论了由制药公司进行的临床前体外测试，以鉴定新药与OCT的相互作用。提出了优化的实验程序，可以无间断地检测抑制性药物和转运药物。