Mammalian nucleoside transporters.

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.