Biol. Pharm. Bull. 30(5) 979—981 (2007)

nucleotide synthesis. Individual nucleosides and nucleobases also serve a variety of specialized functions. Various structural analogues of nucleoside and nucleobase are cytotoxic and have found expanding therapeutic use as antineoplastic agents. Nucleosides and nucleobases are hydrophilic and require specific transporters for permeation through the cell membrane. Several mammalian nucleoside transporters, which are expressed in the plasma membrane of cells, have been cloned. The detailed transport characteristics of human and rat equilibrative nucleoside transporter 2 (hENT2 and rENT2, respectively) have been examined, and they transported a broad range of natural nucleosides and their analogues in Na -independent and nitrobenzylmercaptopurine riboside (NBMPR)-resistant fashions. Furthermore, hENT2 and rENT2 were previously reported to transport not only nucleosides but also purine and pyrimidine nucleobases. However, the transport of nucleosides and nucleobases via mouse ENT2 (mENT2) was not characterized in detail, except for the sensitivity of natural nucleosides and cardioprotective agents to uridine uptake mediated by the transporter. The transport mechanisms of various nucleosides and nucleobases in mouse primary-cultured cells have been investigated. Furthermore, tumor cells-bearing mouse has been used for the developments of improved chemotherapeutic strategies. Therefore, the functional characterization of mENT2 using a variety of nucleosides and nucleobases is physiologically and pharmacologically important. Recently, we clarified that the uracil uptake by mENT2-overexpressing Cos-7 cells (Cos-7/ENT2) for 2 min was similar to that by mock cells (Cos-7/pCI-neo), although uracil was reported to be a substrate for hENT2 and rENT2. These findings hypothesized that there are species differences in transport characteristics of ENT2. In this study, therefore, we evaluated the transport of nucleosides and nucleobases mediated by recombinant mENT2. MATERIALS AND METHODS