Kong Wei, Engel Karen, Wang Joanne
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington 98195 , USA.
Curr Drug Metab. 2004 Feb;5(1):63-84. doi: 10.2174/1389200043489162.
Nucleoside transporters mediate cellular uptake of physiologic nucleosides for nucleic acid synthesis in the salvage pathways in many cell types. These transporters also play an important role in in vivo disposition and intracellular targeting of many nucleoside analogs used in anticancer and antiviral drug therapy. In mammalian cells, there are two major nucleoside transporter gene families: the equilibrative nucleoside transporters (ENTs) and the concentrative nucleoside transporters (CNTs). The ENTs are facilitated carrier proteins and the CNTs are Na(+)-dependent secondary active transporters. Recent molecular cloning of a number of ENT and CNT transporters has greatly advanced our understanding of the molecular and cellular mechanisms by which nucleosides and nucleoside analogs are transported across biological membranes. In this manuscript, we review the structure, function, tissue distribution, and cellular localization of various cloned mammalian nucleoside transporters. Information on transporter interaction with various nucleoside drugs and analogs is presented. Current knowledge on the regulation of nucleoside transporters in various cell types and tissues is reviewed. The therapeutic significance of nucleoside transporters is discussed along with emerging data from recent clinical studies.
核苷转运体介导多种细胞类型补救途径中生理核苷的细胞摄取，用于核酸合成。这些转运体在许多用于抗癌和抗病毒药物治疗的核苷类似物的体内处置和细胞内靶向中也发挥着重要作用。在哺乳动物细胞中，有两个主要的核苷转运体基因家族：平衡核苷转运体（ENTs）和浓缩核苷转运体（CNTs）。ENTs是易化载体蛋白，而CNTs是Na(+)依赖性继发性主动转运体。最近对多种ENT和CNT转运体的分子克隆极大地推进了我们对核苷和核苷类似物跨生物膜转运的分子和细胞机制的理解。在本手稿中，我们综述了各种克隆的哺乳动物核苷转运体的结构、功能、组织分布和细胞定位。还介绍了转运体与各种核苷药物和类似物相互作用的信息。综述了目前关于各种细胞类型和组织中核苷转运体调节的知识。讨论了核苷转运体的治疗意义以及近期临床研究的新数据。
