Mouse equilibrative nucleoside transporter 2 (mENT2) transports nucleosides and purine nucleobases differing from human and rat ENT2

被引:8
作者
Nagai, Katsuhito [1 ]
Nagasawa, Kazuki [1 ]
Kyotani, Yoji [1 ]
Hifumi, Natsuko [1 ]
Fujimoto, Sadaki [1 ]
机构
[1] Kyoto Pharmaceut Univ, Dept Environm Biochem, Yamashina Ku, Kyoto 6078414, Japan
关键词
nucleoside; nucleobase; nucleoside transporter; ENT2; chemotherapy;
D O I
10.1248/bpb.30.979
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Several mammalian nucleoside transporters have been identified at the molecular level. Human and rat equilibrative nucleoside transporter 2 (hENT2 and rENT2, respectively) was previously reported to have the dual ability of transporting both nucleosides and nucleobases. In the present study, we characterized the transport of a variety of nucleosides and nucleobases via recombinant mouse ENT2 (mENT2). Cloned mENT2 mediated the uptake of nucleosides and purine nucleobases, but not pyrimidine nucleobases. The mENT2-mediated uptake of adenosine was significantly inhibited by nucleosides and nucleobases, irrespective of purine and pyrimidine. The K-m values for the uptake of nucleosides and purine nucleobases mediated by mENT2 varied between 1.24 and 16.3 mu m, and the transport clearances of adenosine and hypoxanthine via the transporter were greater than those of other substrates. Therefore, we concluded that mENT2 is nucleoside and purine nucleobase transporter, and pyrimidine nucleobases are blockers for the transporter, differing from hENT2 and rENT2 that were reported to also transport pyrimidine nucleobases.
引用
收藏
页码:979 / 981
页数:3
相关论文
共 21 条
[1]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[2]  
Cass C E, 1999, Pharm Biotechnol, V12, P313
[3]   Recent advances in the molecular biology of nucleoside transporters of mammalian cells [J].
Cass, CE ;
Young, JD ;
Baldwin, SA .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1998, 76 (05) :761-770
[4]  
de Koning H, 2000, MOL MEMBR BIOL, V17, P75
[5]   THE PHYSIOLOGICAL-ROLE OF ADENOSINE IN THE CENTRAL NERVOUS-SYSTEM [J].
DUNWIDDIE, TV .
INTERNATIONAL REVIEW OF NEUROBIOLOGY, 1985, 27 :63-139
[6]   Molecular Cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta [J].
Griffiths, M ;
Yao, SYM ;
Abidi, F ;
Phillips, SEV ;
Cass, CE ;
Young, JD ;
Baldwin, SA .
BIOCHEMICAL JOURNAL, 1997, 328 :739-743
[7]   Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitor-resistant (mENT2) equilibrative nucleoside transporters from mouse brain [J].
Kiss, A ;
Farah, K ;
Kim, J ;
Garriock, RJ ;
Drysdale, TA ;
Hammond, JR .
BIOCHEMICAL JOURNAL, 2000, 352 :363-372
[8]  
Kolb V M, 1997, Prog Drug Res, V48, P195
[9]   Mammalian nucleoside transporters [J].
Kong, W ;
Engel, K ;
Wang, J .
CURRENT DRUG METABOLISM, 2004, 5 (01) :63-84
[10]   Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice [J].
Lu, H ;
Chen, C ;
Klaassen, C .
DRUG METABOLISM AND DISPOSITION, 2004, 32 (12) :1455-1461