Nucleoside transporters: from scavengers to novel therapeutic targets

Trends in Pharmacological Sciences

Volumn 27, Issue 8, 2006, Pages 416-425

  King, Anne E ^a   Ackley, Michael A ^b   Cass, Carol E ^c,d   Young, James D ^c   Baldwin, Stephen A ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^c UNIVERSITY OF ALBERTA   (Canada)

^d CROSS CANCER INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ADENOSINE; ADENOSINE DERIVATIVE; ADENOSINE RECEPTOR BLOCKING AGENT; ADENOSINE RECEPTOR STIMULATING AGENT; ADRENERGIC RECEPTOR BLOCKING AGENT; AMITRIPTYLINE; ANTIINFECTIVE AGENT; ANTIPARASITIC AGENT; ANTIVIRUS AGENT; CLADRIBINE; CYTARABINE; DEOXYCYTIDINE; DILAZEP; DIPYRIDAMOLE; DRAFLAZINE; FLUDARABINE; GEMCITABINE; GUANINE NUCLEOTIDE BINDING PROTEIN; IMIDAZOLINE; MELARSOPROL; MIOFLAZINE; NUCLEOSIDE ANALOG; NUCLEOSIDE TRANSPORTER; PROPENTOFYLLINE; PROTEIN KINASE C INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; RO 316045; UNINDEXED DRUG; VASODILATOR AGENT; ZIDOVUDINE;

ALCOHOLISM; ANALGESIA; AROUSAL; BRAIN TISSUE; CANCER THERAPY; CARDIOVASCULAR DISEASE; HUMAN; NEOPLASM; NOCICEPTION; NONHUMAN; PHYLOGENY; PRIORITY JOURNAL; PROTEIN TRANSPORT; REVIEW; SLEEP; SLEEP DISORDER; SPINAL CORD; SYNAPTIC TRANSMISSION; VIRUS INFECTION;

ANIMALS; HUMANS; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; NUCLEOSIDE TRANSPORT PROTEINS; PHARMACEUTICAL PREPARATIONS;

EID: 33745889935     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tips.2006.06.004     Document Type: Review

References (69)

1. Baldwin S.A., et al. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. 447 (2004) 735-743
2. Gray J.H., et al. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 447 (2004) 728-734
3. De Koning H.P., et al. Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy. FEMS Microbiol. Rev. 29 (2005) 987-1020
4. Mangravite L.M., et al. Nucleoside transporters in the disposition and targeting of nucleoside analogs in the kidney. Eur. J. Pharmacol. 479 (2003) 269-281
5. Ward J.L., et al. Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient PK15 cells. ENT2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine. J. Biol. Chem. 275 (2000) 8375-8381
6. Yao S.Y.M., et al. 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 (2002) 24938-24948
7. Griffiths M., et al. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat. Med. 3 (1997) 89-93
8. Huang M., et al. Inhibition of nucleoside transport by protein kinase inhibitors. J. Pharmacol. Exp. Ther. 304 (2003) 753-760
9. Engel K., and Wang J. Interaction of organic cations with a newly identified plasma membrane monoamine transporter (PMAT). Mol. Pharmacol. 68 (2005) 1397-1407
10. +-coupled nucleoside transporter (hCNT1) produced in Xenopus oocytes. J. Physiol. 558 (2004) 807-823
11. +/nucleoside cotransporter (hCNT3) exhibits novel cation-coupled nucleoside transport characteristics. J. Biol. Chem. 280 (2005) 25436-25449
12. Young J.D., and Jarvis S.M. Nucleoside transport in animal cells. Biosci. Rep. 3 (1983) 309-322
13. Sundaram M., et al. 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 (2001) 45270-45275
14. Sundaram M., et al. 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 (1998) 21519-21525
15. Endres C.J., et al. Mutation of leucine-92 selectively reduces the apparent affinity of inosine, guanosine, NBMPR [S-6-(4-nitrobenzyl)-mercaptopurine riboside] and dilazep for the human equilibrative nucleoside transporter, hENT1. Biochem. J. 380 (2004) 131-137
16. Arastu-Kapur S., et al. Second-site suppression of a nonfunctional mutation within the Leishmania donovani inosine-guanosine transporter. J. Biol. Chem. 280 (2005) 2213-2219
17. Young J.D., et al. Equilibrative (ENT) nucleoside transport proteins. In: Bernhardt I., and Ellory J.C. (Eds). Red Cell Membrane Transport in Health and Disease (2003), Springer-Verlag 321-337
18. +-nucleoside cotransporter rCNT1. J. Biol. Chem. 276 (2001) 27981-27988
19. + nucleoside cotransporters hCNT1 and hCNT2. J. Biol. Chem. 274 (1999) 24475-24484
20. +-nucleoside cotransporter (hfCNT) from the Pacific hagfish (Eptatretus stouti). Am. J. Physiol. Cell Physiol. 283 (2002) C155-C168
21. Cunha R.A. Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem. Int. 38 (2001) 107-125
22. Fredholm B.B., et al. Adenosine and brain function. Int. Rev. Neurobiol. 63 (2005) 191-270
23. Jennings L.L., et al. Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system. Neuropharmacology 40 (2001) 722-731
24. Anderson C.M., et al. Distribution of equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporters (ENT1) in brain. J. Neurochem. 73 (1999) 867-873
25. Anderson C.M., et al. Distribution of mRNA encoding a nitrobenzylthioinosine-insensitive nucleoside transporter (ENT2) in rat brain. Brain Res. Mol. Brain Res. 70 (1999) 293-297
26. Pennycooke M., et al. Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem. Biophys. Res. Commun. 280 (2001) 951-959
27. Porkka-Heiskanen T., et al. Adenosine and sleep. Sleep Med. Rev. 6 (2002) 321-332
28. 1, receptors mediate the arousal effect of caffeine. Nat. Neurosci. 8 (2005) 858-859
29. Porkka-Heiskanen T., et al. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience 99 (2000) 507-517
30. Strecker R.E., et al. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav. Brain Res. 115 (2000) 183-204
31. Mackiewicz M., et al. Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation. J. Neurochem. 85 (2003) 348-357
32. Alanko L., et al. Nitrobenzylthioinosine (NBMPR) binding and nucleoside transporter ENT1 mRNA expression after prolonged wakefulness and recovery sleep in the cortex and basal forebrain of rat. J. Sleep Res. 12 (2003) 299-304
33. Guillen-Gomez E., et al. Distribution of CNT2 and ENT1 transcripts in rat brain: selective decrease of CNT2 mRNA in the cerebral cortex of sleep-deprived rats. J. Neurochem. 90 (2004) 883-893
34. Wauquier A., et al. Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor. Psychopharmacology 91 (1987) 434-439
35. Hack S.P., and Christie M.J. Adaptations in adenosine signaling in drug dependence: therapeutic implications. Crit. Rev. Neurobiol. 15 (2003) 235-274
36. Mailliard W.S., and Diamond I. Recent advances in the neurobiology of alcoholism: the role of adenosine. Pharmacol. Ther. 101 (2004) 39-46
37. Nagy L.E., et al. Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. J. Biol. Chem. 265 (1990) 1946-1951
38. Choi D.S., et al. The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference. Nat. Neurosci. 7 (2004) 855-861
39. Sawynok J., and Liu X.J. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog. Neurobiol. 69 (2003) 313-340
40. 1 receptors reduce release from excitatory but not inhibitory synaptic inputs onto lateral horn neurons. J. Neurosci. 21 (2001) 6308-6320
41. 1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations. Neuroscience 121 (2003) 907-916
42. Lao L.J., et al. Modulation by adenosine of Aδ and C primary-afferent glutamatergic transmission in adult rat substantia gelatinosa neurons. Neuroscience 125 (2004) 221-231
43. Yan L., et al. Adenosine receptor agonists: from basic medicinal chemistry to clinical development. Expert Opin. Emerg. Drugs 8 (2003) 537-576
44. Ackley M.A., et al. Control of glutamatergic neurotransmission in the rat spinal dorsal horn by the nucleoside transporter ENT1. J. Physiol. 548 (2003) 507-517
45. Governo R.J., et al. Localization of the NBMPR-sensitive equilibrative nucleoside transporter, ENT1, in the rat dorsal root ganglion and lumbar spinal cord. Brain Res. 1059 (2005) 129-138
46. Liu T., et al. Regulation by equilibrative nucleoside transporter of adenosine outward currents in adult rat spinal dorsal horn neurons. Brain Res. Bull. 64 (2004) 75-83
47. Raghavendra V., et al. Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Pain 104 (2003) 655-664
48. Sawynok J., et al. Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake. Eur. J. Pharmacol. 518 (2005) 116-122
49. Ackley M.A., et al. Adenosine contributes to μ-opioid synaptic inhibition in rat substantia gelatinosa in vitro. Neurosci. Lett. 376 (2005) 102-106
50. 1 adenosine receptor. Anesthesiology 102 (2005) 416-420
51. Keil G.J., and DeLander G.E. Time-dependent antinociceptive interactions between opioids and nucleoside transport inhibitors. J. Pharmacol. Exp. Ther. 274 (1995) 1387-1392
52. Van Belle H. Nucleoside transport inhibition - a therapeutic approach to cardioprotection via adenosine?. Cardiovasc. Res. 27 (1993) 68-76
53. Musa H., et al. Immunocytochemical demonstration of the equilibrative nucleoside transporter rENT1 in rat sinoatrial node. J. Histochem. Cytochem. 50 (2002) 305-309
54. Meester B.J., et al. Pharmacological analysis of the activity of the adenosine uptake inhibitor, dipyridamole, on the sinoatrial and atrioventricular nodes of the guinea-pig. Br. J. Pharmacol. 124 (1998) 729-741
55. Masuda M., et al. Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts. J. Thorac. Cardiovasc. Surg. 104 (1992) 1610-1617
56. Galmarini C.M., et al. Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol. 3 (2002) 415-424
57. Marks K., and Gulick R.M. New antiretroviral agents for the treatment of HIV infection. Curr. Infect. Dis. Rep. 6 (2004) 333-339
58. Clarke M.L., et al. The role of membrane transporters in cellular resistance to anticancer nucleoside drugs. Cancer Treat. Res. 112 (2002) 27-47
59. Damaraju V.L., et al. Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy. Oncogene 22 (2003) 7524-7536
60. Pastor-Anglada M., et al. Cell entry and export of nucleoside analogues. Virus Res. 107 (2005) 151-164
61. Spratlin J., et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin. Cancer Res. 10 (2004) 6956-6961
62. Damaraju S., et al. Identification and functional characterization of variants in human concentrative nucleoside transporter 3, hCNT3 (SLC28A3), arising from single nucleotide polymorphisms in coding regions of the hCNT3 gene. Pharmacogenet. Genomics 15 (2005) 173-182
63. Urban T.J., et al. Functional genomics of membrane transporters in human populations. Genome Res. 16 (2006) 223-230
64. Geiser F., et al. Molecular pharmacology of adenosine transport in Trypanosoma brucei: P1/P2 revisited. Mol. Pharmacol. 68 (2005) 589-595
65. el Kouni M.H. Potential chemotherapeutic targets in the purine metabolism of parasites. Pharmacol. Ther. 99 (2003) 283-309
66. Baldwin S.A., et al. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J. Biol. Chem. 280 (2005) 15880-15887
67. +-nucleoside cotransporter (hCNT1). Am. J. Physiol. 272 (1997) C707-C714
68. +/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol. Membr. Biol. 15 (1998) 203-211
69. +-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J. Biol. Chem. 276 (2001) 2914-2927