Functional and molecular characteristics of Na+-dependent nucleoside transporters

Nucleoside transporters play a critical role in the absorption, disposition, and targeting of therapeutically used nucleosides and nucleoside analogs. This review is focused on the Nac-dependent, concentrative nucleoside transporters which are found in a variety of cells including renal, intestinal and hepatic epithelia. Five major Na+-dependent nucleoside transporter subtypes have been characterized in isolated tissue preparations: N1 is purine selective; N2 is pyrimidine selective and N3-N5 exhibit variable selectivity for both purine and pyrimidine nucleosides. The recent cloning of N1 and N2 nucleoside transporters has provided the first information on the molecular function and structure of concentrative nucleoside transporters. In this manuscript we review the characteristics of the various subtypes of nucleoside transporters and the molecular structure, functional properties, and tissue distribution of the cloned Na+-dependent nucleoside transporters. In addition, the interactions of nucleosides and nucleoside analogs with the cloned transporters in mammalian and amphibian expression systems are presented. Mammalian expression systems may be particularly useful during drug development in screening potential compounds for improved bioavailability and tissue specific targeting. Finally, we present our view of future areas of study in the field of nucleoside transporters.