Nucleoside Transporters (SLC28 and SLC29) Family

Pharmacogenomics of Human Drug Transporters: Clinical Impacts

Volumn , Issue , 2013, Pages 243-270

  Molina Arcas, Míriam ^a   Pastor Anglada, Marçal ^b  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Cancer; Drugs; HCNT; HENT; Nucleosides; SLC28; SLC29; Viral diseases

Indexed keywords

EID: 84886137432     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118353240.ch11     Document Type: Chapter

References (113)

1. Aran JM, Plagemann PG (1992) Nucleoside transport-deficient mutants of PK-15 pig kidney cell line. Biochim Biophys Acta, 1110, 51-58.
2. Aymerich I, Pastor-Anglada M, Casado FJ (2004) Long term endocrine regulation of nucleoside transporters in rat intestinal epithelial cells. J Gen Physiol, 124, 505-512.
3. Badagnani I, Chan W, Castro RA, Brett CM, Huang CC, Stryke D, Kawamoto M, Johns SJ, Ferrin TE, Carlson EJ, Burchard EG, Giacomini KM (2005) Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3) . Pharmacogenomics J, 5, 157-165.
4. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch, 447, 735-743.
5. Baldwin SA, Yao SY, Hyde RJ, Ng AM, Foppolo S, Barnes K, Ritzel MW, Cass CE, Young JD (2005) Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem, 280, 15880-15887.
6. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel MW, Claycomb WC, et al. (2006) Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res, 99, 510-519.
7. Cano-Soldado P, Pastor-AngladaM (2012) Transporters that translocate nucleosides and structural similar drugs: structural requirements for substrate recognition. Med Res Rev, 32, 428-457.
8. Cano-Soldado P, Lorrayoz IM, Molina-Arcas M, Casado FJ, Martinez-Picado J, Lostao MP, Pastor-Anglada M (2004) Interaction of nucleoside inhibitors of HIV-1 reverse transcriptase with the concentrative nucleoside transporter-1 (SLC28A1) . Antivir Ther, 9, 993-1002.
9. Cansev M (2006) Uridine and cytidine in the brain: their transport and utilization. Brain Res Rev, 52, 389-397.
10. Cliffe ST, Kramer JM, Hussain K, Robben JH, de Jong EK, de Brouwer AP, Nibbeling E, Kamsteeg EJ, Wong M, Prendiville J, et al. (2009) SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway. Hum Mol Genet, 18, 2257-2265.
11. Damaraju VL, Smith KM, Mowles D, Nowak I, Karpinski E, Young JD, Robins MJ, Cass CE (2011) Interaction of fused-pyrimidine nucleoside analogs with human concentrative nucleoside transporters: high-affinity inhibitors of human concentrative nucleoside transporter 1. Biochem Pharmacol, 81, 82-90.
12. Deval J (2009) Antimicrobial strategies: inhibition of viral polymerases by 3-hydroxyl nucleosides. Drugs, 69, 151-166.
13. Doehring A, Hofmann WP, Schlecker C, Zeuzem S, Sarrazin C, Berg T, Muller T, Herrmann E, Geisslinger G, Lotsch J (2011) Role of nucleoside transporters SLC28A2/3 and SLC29A1/2 genetics in ribavirin therapy: protection against anemia in patients with chronic hepatitis C. Pharmacogenet Genomics, 21, 289-296.
14. Duflot S, Calvo M, Casado FJ, Enrich C, Pastor-Anglada M (2002) Concentrative nucleoside transporter (rCNT1) is targeted to the apical membrane through the hepatic transcytotic pathway. Exp Cell Res, 281, 77-85.
15. Endres CJ, Moss AM, Govindarajan R, Choi DS, Unadkat JD (2009) The role of nucleoside transporters in the erythrocyte disposition and oral absorption of ribavirin in the wild-type and equilibrative nucleoside transporter 1-/-mice. J Pharmacol Exp Ther, 331, 287-296.
16. Errasti-Murugarren E, Cano-Soldado P, Pastor-Anglada M, Casado FJ (2008) Functional characterization of a nucleoside-derived drug transporter variant (hCNT3C602R) showing altered sodium-binding capacity. Mol Pharmacol, 73, 379-386.
17. Errasti-Murugarren E, Molina-Arcas M, Casado FJ, Pastor-Anglada M (2010) The human concentrative nucleoside transporter-3 C602R variant shows impaired sorting to lipid rafts and altered specificity for nucleoside-derived drugs. Mol Pharmacol, 78, 157-165.
18. Errasti-Murugarren E, Pastor-Anglada M (2010) Drug transporter pharmacogenetics in nucleoside-based therapies. Pharmacogenomics, 11, 809-841.
19. Errasti-Murugarren E, Pastor-Anglada M, Casado FJ (2007) Role of Cnt3 in the transepithelial flux of nucleosides and nucleoside-derived drugs. J Physiol, 582 (Pt 3), 1249-1260.
20. Farre X, Guillen-Gomez E, Sanchez L, Hardisson D, Plaza Y, Lloberas J, Casado FJ, Palacios J, Pastor-Anglada M (2004) Expression of the nucleoside-derived drug transporters hCNT1, hENT1 and hENT2 in gynecologic tumors. Int J Cancer, 112, 959-966.
21. Fernandez-Calotti P, Pastor-Anglada M (2010) All-trans-retinoic acid promotes trafficking of human concentrative nucleoside transporter-3 (hCNT3) to the plasma membrane by a TGF-beta1-mediated mechanism. J Biol Chem, 285, 13589-13598.
22. Fotoohi AK, Lindqvist M, Peterson C, Albertioni F (2006) Involvement of the concentrative nucleoside transporter 3 and equilibrative nucleoside transporter 2 in the resistance of T-lymphoblastic cell lines to thiopurines. Biochem Biophys Res Commun, 343, 208-215.
23. Gati WP, Paterson AR, Larratt LM, Turner AR, Belch AR (1997) Sensitivity of acute leukemia cells to cytarabine is a correlate of cellular es nucleoside transporter site content measured by flow cytometry with SAENTA-fluorescein. Blood, 90, 346-353.
24. Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, Orlandini C, Boggi U, Campani D, Del Chiaro M, et al. (2006) Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res, 66, 3928-3935.
25. Gloeckner-Hofmann K, Guillen-Gomez E, Schmidtgen C, Porstmann R, Ziegler R, Stoss O, Casado FJ, Ruschoff J, Pastor-Anglada M (2006) Expression of the high-affinity fluoropyrimidine-preferring nucleoside transporter hCNT1 correlates with decreased disease-free survival in breast cancer. Oncology, 70, 238-244.
26. Govindarajan R, Bakken AH, Hudkins KL, Lai Y, Casado FJ, Pastor-Anglada M, Tse CM, Hayashi J, Unadkat JD (2007) In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta. Am J Physiol Regul Integr Comp Physiol, 293, R1809-R1822.
27. Govindarajan R, Endres CJ, Whittington D, LeCluyse E, Pastor-Anglada M, Tse CM, Unadkat JD (2008) Expression and hepatobiliary transport characteristics of the concentrative and equilibrative nucleoside transporters in sandwich-cultured human hepatocytes. Am J Physiol Gastrointest Liver Physiol, 295, G570-G580.
28. Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD (2009) Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol, 296, G910-G922.
29. Gray JH, Mangravite LM, Owen RP, Urban TJ, Chan W, Carlson EJ, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, Giacomini KM (2004a) Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol Pharmacol, 65, 512-519.
30. Gray JH, Owen RP, Giacomini KM (2004b) The concentrative nucleoside transporter family, SLC28. Pflugers Arch, 447, 728-734.
31. Gupte A, Buolamwini JK (2009) Synthesis and biological evaluation of phloridzin analogs as human concentrative nucleoside transporter 3 (hCNT3) inhibitors. Bioorg Med Chem Lett, 19, 917-921.
32. Hamilton SR, Yao SY, Ingram JC, Hadden DA, Ritzel MW, Gallagher MP, Henderson PJ, Cass CE, Young JD, Baldwin SA (2001) Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1. J Biol Chem, 276, 27981-27988.
33. Hsu LS (1982) The kinetics of uptake of 5-fluorouracil by rat liver. Br J Pharmacol, 77, 413-417.
34. Hu H, Endres CJ, Chang C, Umapathy NS, Lee EW, Fei YJ, Itagaki S, Swaan PW, Ganapathy V, Unadkat JD (2006) Electrophysiological characterization and modeling of the structure activity relationship of the human concentrative nucleoside transporter 3 (hCNT3) . Mol Pharmacol, 69, 1542-1553.
35. Hubeek I, Stam RW, Peters GJ, Broekhuizen R, Meijerink JP, van Wering ER, Gibson BE, Creutzig U, Zwaan CM, Cloos J, Kuik DJ, Pieters R, Kaspers GJ (2005) The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br J Cancer, 93, 1388-1394.
36. Hyde RJ, Cass CE, Young JD, Baldwin SA (2001) The ENT family of eukaryote nucleoside and nucleobase transporters: recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol, 18, 53-63.
37. Johnson SA (2001) Nucleoside analogues in the treatment of haematological malignancies. Expert Opin Pharmacother, 2, 929-943.
38. Johnson ZL, Cheong CG, Lee SY (2012) Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4A° . Nature, 483 (7390), 489-93.
39. Kim JH, Karpyak VM, Biernacka JM, Nam HW, Lee MR, Preuss UW, Zill P, Yoon G, Colby C, Mrazek DA, Choi DS (2011) Functional role of the polymorphic 647 T/C variant of ENT1 (SLC29A1) and its association with alcohol withdrawal seizures. PLoS One, 6, e16331.
40. King K, Damaraju V, Vickers M, Yao S, Lang T, Tackaberry T, Mowles D, Ng A, Young J, Cass C (2006) A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine and fludarabine by recombinant human nucleoside transporters produced in three model expression systems. Mol Pharmacol, 69, 346-353.
41. Lai Y, Bakken AH, Unadkat JD (2002) Simultaneous expression of hCNT1-CFP and hENT1-YFP in Madin-Darby canine kidney cells. Localization and vectorial transport studies. J Biol Chem, 277, 37711-37717.
42. Lai Y, Tse CM, Unadkat JD (2004) Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. J Biol Chem, 279, 4490-4497.
43. Lane J, Martin TA, McGuigan C, Mason MD, Jiang WG (2010) The differential expression of hCNT1 and hENT1 i n breast cancer and the possible impact on breast cancer therapy. J Exp Ther Oncol, 8, 203-210.
44. Lang TT, Selner M, Young JD, Cass CE (2001) Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Mol Pharmacol, 60, 1143-1152.
45. Larrayoz IM, Casado FJ, Pastor-Anglada M, Lostao MP (2004) Electrophysiological characterization of the human Na (+) /nucleoside cotransporter 1 (hCNT1) and role of adenosine on hCNT1 function. J Biol Chem, 279, 8999-9007.
46. Lee EW, Lai Y, Zhang H, Unadkat JD (2006) Identification of the mitochondrial targeting signal of the human equilibrative nucleoside transporter 1 (hENT1): implications for interspecies differences in mitochondrial toxicity of fialuridine. J Biol Chem, 281, 16700-16706.
47. Li JY, Boado RJ, Pardridge WM (2001) Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J Cereb Blood Flow Metab, 21, 929-936.
48. Li L, Koo SH, Hong IH, Lee EJ (2009) Identification of functional promoter haplotypes of human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) . Drug Metab Pharmacokinet, 24, 161-166.
49. Li L, Tan CM, Koo SH, Chong KT, Lee EJ (2007) Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians. Pharmacogenet Genomics, 17, 783-786.
50. Loewen SK, Ng AM, Yao SY, Cass CE, Baldwin SA, Young JD (1999) Identification of amino acid residues responsible for the pyrimidine and purine nucleoside specificities of human concentrative Na (+) nucleoside cotransporters hCNT1 and hCNT2. J Biol Chem, 274, 24475-24484.
51. Loewen SK, Yao SY, Slugoski MD, Mohabir NN, Turner RJ, Mackey JR, Weiner JH, Gallagher MP, Henderson PJ, Baldwin SA, Cass CE, Young JD (2004) Transport of physiological nucleosides and anti-viral and anti-neoplastic nucleoside drugs by recombinant Escherichia coli nucleoside-H (+) cotransporter (NupC) produced in Xenopus laevis oocytes. Mol Membr Biol, 21, 1-10.
52. Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer, 3, 330-338.
53. Mackey JR, Galmarini CM, Graham KA, Joy AA, Delmer A, Dabbagh L, Glubrecht D, Jewell LD, Lai R, Lang T, Hanson J, Young JD, Merle-Béral H, Binet JL, Cass CE, Dumontet C (2005) Quantitative analysis of nucleoside transporter and metabolism gene expression in chronic lymphocytic leukemia (CLL): identification of fludarabine-sensitive and -insensitive populations. Blood, 105, 767-774.
54. Mackey JR, Jennings LL, Clarke ML, Santos CL, Dabbagh L, Vsianska M, Koski SL, Coupland RW, Baldwin SA, Young JD, Cass CE (2002) Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. Clin Cancer Res, 8, 110-116.
55. Mackey JR, Mani RS, Selner M, Mowles D, Young JD, Belt JA, Crawford CR, Cass CE (1998) Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res, 58, 4349-4357.
56. Mangravite LM, Giacomini KM (2003) Sorting of rat SPNT in renal epithelium is independent of Nglycosylation. Pharm Res, 20, 319-323.
57. Mangravite LM, Lipschutz JH, Mostov KE, Giacomini KM (2001) Localization of GFP-tagged concentrative nucleoside transporters in a renal polarized epithelial cell line. Am J Physiol Renal Physiol, 280, F879-F885.
58. Mani RS, Hammond JR, Marjan JM, Graham KA, Young JD, Baldwin SA, Cass CE (1998) Demonstration of equilibrative nucleoside transporters (hENT1 and hENT2) in nuclear envelopes of cultured human choriocarcinoma (BeWo) cells by functional reconstitution in proteoliposomes. J Biol Chem, 273, 30818-30825.
59. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D (2006) Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica, 91, 895-902.
60. Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Young J, Salmon I, Deviere J, Van Laethem JL (2009) Human equilibrative nucleoside transporter 1 and human concentrative nucleoside transporter 3 predict survival after adjuvant gemcitabine therapy in resected pancreatic adenocarcinoma. Clin Cancer Res, 15, 2913-2919.
61. Marvi M, Rose JB, Bang A, Moon BC, Pozeg Z, Ibrahim M, Peniston C, Coe IR (2010) Nucleoside transporter expression profiles in human cardiac tissue show striking individual variability with overall predominance of hENT1. Eur J Pharm Sci, 41, 685-691.
62. Mata JF, Garcia-Manteiga JM, Lostao MP, Fernandez-Veledo S, Guillen-Gomez E, Larrayoz IM, Lloberas J, Casado FJ, Pastor-Anglada M (2001) Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol, 59, 1542-1548.
63. Minuesa G, Purcet S, Erkizia I, Molina-Arcas M, Bofill M, Izquierdo-Useros N, Casado FJ, Clotet B, Pastor-Anglada M, Martinez-Picado J (2008) Expression and functionality of anti-human immunodeficiency virus and anticancer drug uptake transporters in immune cells. J Pharmacol Exp Ther, 324, 558-567.
64. Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, Elpeleg O, Zlotogorski A (2008) The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet, 83, 529-534.
65. Molina-Arcas M, Bellosillo B, Casado FJ, Montserrat E, Gil J, Colomer D, Pastor-Anglada M (2003) Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia. Blood, 101, 2328-2334.
66. Myers SN, Goyal RK, Roy JD, Fairfull LD, Wilson JW, Ferrell RE (2006) Functional single nucleotide polymorphism haplotypes in the human equilibrative nucleoside transporter 1. Pharmacogenet Genomics, 16, 315-320.
67. Naito T, Tokashiki S, Mino Y, Otsuka A, Ozono S, Kagawa Y, Kawakami J (2010) Impact of concentrative nucleoside transporter 1 gene polymorphism on oral bioavailability of mizoribine in stable kidney transplant recipients. Basic Clin Pharmacol Toxicol, 106, 310-316.
68. Nakamura J, Horimoto T, Hirayama R, Mukai T, Nakashima M, Sasaki H, Nishida K (2003) Effect of the absorption enhancer saponin on the intrarenal distribution of 5-fluorouracil following its kidney surface application in rats. Biol Pharm Bull, 26, 1049-1051.
69. Okazaki T, Javle M, Tanaka M, Abbruzzese JL, Li D (2010) Single nucleotide polymorphisms of gemcitabine metabolic genes and pancreatic cancer survival and drug toxicity. Clin Cancer Res, 16, 320-329.
70. Osses N, Pearson JD, Yudilevich DL, Jarvis SM (1996) Hypoxanthine enters human vascular endothelial cells (ECV 304) via the nitrobenzylthioinosine-insensitive equilibrative nucleoside transporter. Biochem J, 317, 843-848.
71. Owen RP, Badagnani I, Giacomini KM (2006a) Molecular determinants of specificity for synthetic nucleoside analogs in the concentrative nucleoside transporter, CNT2. J Biol Chem, 281, 26675-26682.
72. Owen RP, Gray JH, Taylor TR, Carlson EJ, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, Giacomini KM (2005) Genetic analysis and functional characterization of polymorphisms in the human concentrative nucleoside transporter, CNT2. Pharmacogenet Genomics, 15, 83-90.
73. Owen RP, Lagpacan LL, Taylor TR, De La Cruz M, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, Giacomini KM (2006b) Functional characterization and haplotype analysis of polymorphisms in the human equilibrative nucleoside transporter, ENT2. Drug Metab Dispos, 34, 12-15.
74. Pastor-Anglada M, Errasti-Murugarren E, Aymerich I, Casado FJ (2007) Concentrative Nucleoside Transporters (CNTs) in epithelia: from absorption to cell signalling. J Physiol Biochem, 63, 97-110.
75. Pennycooke M, Chaudary N, Shuralyova I, Zhang Y, Coe IR (2001) Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem Biophys Res Commun, 280, 951-959.
76. Rabascio C, Laszlo D, Andreola G, Saronni L, Radice D, Rigacci L, Fabbri A, Frigeri F, Calabrese L, Billio A, Bertolini F, Martinelli G (2010) Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenstrom's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2-deoxyadenosine (2-CdA) and Rituximab. Leuk Res, 34, 454-457.
77. Ritzel MW, Ng AM, Yao SY, Graham K, Loewen SK, Smith KM, Ritzel RG, Mowles DA, Carpenter P, Chen XZ, Karpinski E, Hyde RJ, Baldwin SA, Cass CE, Young JD (2001) Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib) . J Biol Chem, 276, 2914-2927.
78. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD (1997) Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1) . Am J Physiol, 272, C707-C714.
79. Ritzel MW, Yao SY, Ng AM, Mackey JR, Cass CE, Young JD (1998) Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol Membr Biol, 15, 203-211.
80. Robak T, Korycka A, Lech-Maranda E, Robak P (2009) Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules, 14, 1183-1226.
81. Sahasranaman S, Howard D, Roy S (2008) Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol, 64, 753-767.
82. Saiko P, Horvath Z, Jaeger W, Schott H, Fritzer-Szekeres M, Szekeres T (2005) Heterodinucleoside phosphates of 5-fluorodeoxyuridine and arabinofuranosylcytosine-new drugs in cancer chemotherapy?. In Vivo, 19, 205-214.
83. SenGupta DJ, Unadkat JD (2004) Glycine 154 of the equilibrative nucleoside transporter, hENT1, is important for nucleoside transport and for conferring sensitivity to the inhibitors nitrobenzylthioinosine, dipyridamole, and dilazep. Biochem Pharmacol, 67, 453-458.
84. Slugoski MD, Loewen SK, Ng AM, Smith KM, Yao SY, Karpinski E, Cass CE, Baldwin SA, Young JD (2007) Specific mutations in transmembrane helix 8 of human concentrative Na+/nucleoside cotransporter hCNT1 affect permeant selectivity and cation coupling. Biochemistry, 46, 1684-1693.
85. Slugoski MD, Ng AM, Yao SY, Lin CC, Mulinta R, Cass CE, Baldwin SA, Young JD (2009) Substituted cysteine accessibility method analysis of human concentrative nucleoside transporter hCNT3 reveals a novel discontinuous region of functional importance within the CNT family motif (G/A) XKX3NEFVA (Y/M/F) . J Biol Chem, 284, 17281-17292.
86. Smith KM, Ng AM, Yao SY, Labedz KA, Knaus EE, Wiebe LI, Cass CE, Baldwin SA, Chen XZ, Karpinski E, Young JD (2004) Electrophysiological characterization of a recombinant human Na+-coupled nucleoside transporter (hCNT1) produced in Xenopus oocytes. J Physiol, 558, 807-823.
87. Smith KM, Slugoski MD, Loewen SK, Ng AM, Yao SY, Chen XZ, Karpinski E, Cass CE, Baldwin SA, Young JD (2005) The broadly selective human Na+/nucleoside cotransporter (hCNT3) exhibits novel cation-coupled nucleoside transport characteristics. J Biol Chem, 280, 25436-25449.
88. Soler C, Felipe A, Casado FJ, Celada A, Pastor-Anglada M (2000) Nitric oxide regulates nucleoside transport in activated B lymphocytes. J Leukoc Biol, 67, 345-349.
89. Soler C, Felipe A, Mata JF, Casado FJ, Celada A, Pastor-AngladaM (1998) Regulation of nucleoside transport by lipopolysaccharide, phorbol esters, and tumor necrosis factor-alpha in human B-lymphocytes. J Biol Chem, 273, 26939-26945.
90. Soler C, Garcia-Manteiga J, Valdes R, Xaus J, Comalada M, Casado FJ, Pastor-Anglada M, Celada A, Felipe A (2001a) Macrophages require different nucleoside transport systems for proliferation and activation. FASEB J, 15, 1979-1988.
91. Soler C, Valdés R, Garcia-Manteiga J, Xaus J, Comalada M, Casado FJ, Modolell M, Nicholson B, MacLeod C, Felipe A, Celada A, Pastor-Anglada M (2001b) Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation of concentrative nucleoside transporters Cnt1 and Cnt2 through tumor necrosis factor-alpha-dependent and -independent mechanisms. JBiolChem, 276, 30043-30049.
92. Soo RA, Wang LZ, Ng SS, Chong PY, Yong WP, Lee SC, Liu JJ, Choo TB, Tham LS, Lee HS, Goh BC, Soong R (2009) Distribution of gemcitabine pathway genotypes in ethnic Asians and their association with outcome in non-small cell lung cancer patients. Lung Cancer, 63, 121-127.
93. Spiegel R, Cliffe ST, Buckley MF, Crow YJ, Urquhart J, Horovitz Y, Tenenbaum-Rakover Y, Newman WG, Donnai D, Shalev SA (2010) Expanding the clinical spectrum of SLC29A3 gene defects. Eur J Med Genet, 53, 309-313.
94. Spratlin J, Sangha R, Glubrecht D, Dabbagh L, Young JD, Dumontet C, Cass C, Lai R, Mackey JR (2004) The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res, 10, 6956-6961.
95. Sundaram M, Yao SY, Ingram JC, Berry ZA, Abidi F, Cass CE, Baldwin SA, Young JD (2001a) Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR) -sensitive nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and anti-cancer drugs. J Biol Chem, 276, 45270-45275.
96. Sundaram M, Yao SY, Ng AM, Cass CE, Baldwin SA, Young JD (2001b) Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins. Biochemistry, 40, 8146-8151.
97. Sundaram M, Yao SY, Ng AM, Griffiths M, Cass CE, Baldwin SA, Young JD (1998) Chimeric constructs between human and rat equilibrative nucleoside transporters (hENT1 and rENT1) reveal hENT1 structural domains interacting with coronary vasoactive drugs. J Biol Chem, 273, 21519-21525.
98. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H (2002) Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther, 300, 918-924.
99. Tanaka M, Javle M, Dong X, Eng C, Abbruzzese JL, Li D (2010) Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer. Cancer, 116, 5325-5335.
100. Tozzi V (2010) Pharmacogenetics of antiretrovirals. Antiviral Res, 85, 190-200. Valdes R, Arastu-Kapur S, Landfear SM, Shinde U (2009) An ab Initio structural model of a nucleoside permease predicts functionally important residues. J Biol Chem, 284, 19067-19076.
101. Vickers MF, Mani RS, Sundaram M, Hogue DL, Young JD, Baldwin SA, Cass CE (1999) Functional production and reconstitution of the human equilibrative nucleoside transporter (hENT1) in Saccharomyces cerevisiae, Interaction of inhibitors of nucleoside transport with recombinant hENT1 and a glycosylation-defective derivative (hENT1/N48Q) . Biochem J, 339 (Pt 1), 21-32.
102. Visser F, Vickers MF, Ng AM, Baldwin SA, Young JD, Cass CE (2002) Mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sensitivity to inhibition of transport by dilazep and dipyridamole. J Biol Chem, 277, 395-401.
103. Wang C, Pimple S, Buolamwini JK (2010) Interaction of benzopyranone derivatives and related compounds with human concentrative nucleoside transporters 1, 2 and 3 heterologously expressed in porcine PK15 nucleoside transporter deficient cells. Structure-activity relationships and determinants of transporter affinity and selectivity. Biochem Pharmacol, 79, 307-320.
104. Wang J, Giacomini KM (1997) Molecular determinants of substrate selectivity in Na+-dependent nucleoside transporters. J Biol Chem, 272, 28845-28848.
105. Ward JL, Leung GP, Toan SV, Tse CM (2003) Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2. Arch Biochem Biophys, 411, 19-26.
106. Ward JL, Sherali A, Mo ZP, Tse CM (2000) Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporterdeficient PK15 cells. Ent2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine. J Biol Chem, 275, 8375-8381.
107. Wong A, Soo RA, Yong WP, Innocenti F (2009) Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev, 41, 77-88.
108. Wright AM, Paterson AR, Sowa B, Akabutu JJ, Grundy PE, Gati WP (2002) Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in leukaemic lymphoblasts from paediatric patients: significance of cellular nucleoside transporter content. Br J Haematol, 116, 528-537.
109. Yamamoto T, Sugawara M, Kikukawa T, Miyauchi S, Yamaguchi M, Tero A, Takagi S, Nakagaki T (2010) Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes. Biophys Chem, 147, 59-65.
110. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD (2001) Transport of antiviral 3-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR) -insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol, 18, 161-167.
111. Yao SY, Ng AM, Vickers MF, Sundaram M, Cass CE, Baldwin SA, Young JD (2002) Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation. J Biol Chem, 277, 24938-24948.
112. Yee SW, Shima JE, Hesselson S, Nguyen L, De Val S, Lafond RJ, Kawamoto M, Johns SJ, Stryke D, Kwok PY, et al. (2009) Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2) . J Pharmacol Exp Ther, 328, 699-707.
113. Zhang J, Visser F, Vickers MF, Lang T, Robins MJ, Nielsen LP, Nowak I, Baldwin SA, Young JD, Cass CE (2003) Uridine binding motifs of human concentrative nucleoside transporters 1 and 3 produced in Saccharomyces cerevisiae. Mol Pharmacol, 64, 1512-1520.