Division of Applied Medicine, Kosterlitz Centre for Therapeutics, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland, UK.
Amino Acids. 2014 Mar;46(3):655-60. doi: 10.1007/s00726-013-1553-6. Epub 2013 Jul 13.
In recent years, our understanding of the importance of membrane transporters (MTs) in the disposition of and response to drugs has increased significantly. MTs are proteins that regulate the transport of endogenous molecules and xenobiotics across the cell membrane. In mammals, two super-families have been identified: ATP-binding cassette (ABC) and solute carrier (SLC) transporters. There is evidence that MTs might mediate polyamines (PA) transport. PA are ubiquitous polycations which are found in all living cells. In mammalian cells, three major PA are synthesised: putrescine, spermidine and spermine; whilst the decarboxylated arginine (agmatine) is not produced by mammals but is synthesised by plants and bacteria. In addition, research in the PA field suggests that PA are transported into cells via a specific transporter, the polyamine transport system(s) (PTS). Although the PTS has not been fully defined, there is evidence that some of the known MTs might be involved in PA transport. In this mini review, eight SLC transporters will be reviewed and their potential to mediate PA transport in human cells discussed. These transporters are SLC22A1, SLC22A2, SLC22A3, SLC47A1, SLC7A1, SLC3A2, SLC12A8A, and SLC22A16. Preliminary data from our laboratory have revealed that SLC22A1 might be involved in the PA uptake; in addition to one member of ABC superfamily (MDR1 protein) might also mediate the efflux of polyamine like molecules.
近年来，我们对膜转运体（MTs）在药物处置和反应中的重要性的理解有了显著提高。MTs 是调节内源性分子和外源性物质跨细胞膜转运的蛋白质。在哺乳动物中，已经鉴定出两个超家族：ATP 结合盒（ABC）和溶质载体（SLC）转运体。有证据表明 MTs 可能介导多胺（PA）的转运。PA 是普遍存在的多阳离子，存在于所有活细胞中。在哺乳动物细胞中，三种主要的 PA 是腐胺、精胺和精脒；而脱羧精氨酸（胍丁胺）不是哺乳动物产生的，而是由植物和细菌合成的。此外，PA 领域的研究表明，PA 通过特定的转运体，即多胺转运系统（PTS）进入细胞。尽管 PTS 尚未完全定义，但有证据表明一些已知的 MTs 可能参与 PA 的转运。在这篇迷你综述中，将对八种 SLC 转运体进行综述，并讨论它们在人类细胞中转运 PA 的潜力。这些转运体是 SLC22A1、SLC22A2、SLC22A3、SLC47A1、SLC7A1、SLC3A2、SLC12A8A 和 SLC22A16。我们实验室的初步数据表明，SLC22A1 可能参与 PA 的摄取；此外，ABC 超家族的一个成员（MDR1 蛋白）也可能介导多胺样分子的外排。
