Uridine function in the central nervous system

Current Topics in Medicinal Chemistry

Volumn 11, Issue 8, 2011, Pages 1058-1067

  Dobolyi, Arpád ^a   Juhász, Gábor ^b   Kovács, Zsolt ^c   Kardos, Julianna ^d  

^a INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^b EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^c UNIVERSITY OF WEST HUNGARY   (Hungary)

^d CHEMICAL RESEARCH CENTER   (Hungary)

Author keywords

Epilepsy; Neural function; Neuronal plasticity; Nucleoside transport; Nucleotide receptor; Pyrimidine salvage; Sleep; Therapeutic application

Indexed keywords

CITICOLINE; DRUG RECEPTOR; HALOPERIDOL; PYRIMIDINE; URIDINE;

ARTICLE; CENTRAL NERVOUS SYSTEM DISEASE; CENTRAL NERVOUS SYSTEM FUNCTION; DEGENERATIVE DISEASE; DIET SUPPLEMENTATION; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG MEGADOSE; DRUG METABOLISM; EPILEPSY; HUMAN; MEMBRANE FORMATION; MEMORY CONSOLIDATION; MOOD CHANGE; NERVE CELL MEMBRANE; NERVE CELL PLASTICITY; NONHUMAN; SLEEP; THERMOREGULATION;

ADULT; ANIMALS; CENTRAL NERVOUS SYSTEM; EPILEPSY; HUMANS; MEMORY; MICE; NEURODEGENERATIVE DISEASES; NEUROGLIA; NEURONAL PLASTICITY; NEURONS; NEUROPROTECTIVE AGENTS; PURINERGIC P2 RECEPTOR AGONISTS; PURINERGIC P2 RECEPTOR ANTAGONISTS; RATS; RECEPTORS, PURINERGIC P2Y; SLEEP; URACIL NUCLEOTIDES; URIDINE;

EID: 79954537758     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802611795347618     Document Type: Article

References (132)

1. Yegutkin, G. G. Nucleotide-and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim. Biophys. Acta-Mol. Cell. Res., 2008, 1783, 673-694.
2. Burnstock, G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev., 2007, 87, 659-797.
3. Rose, J. B.; Coe, I. R. Physiology of nucleoside transporters: back to the future. Physiology, (Bethesda) 2008, 23, 41-48.
4. Cansev, M. Uridine and cytidine in the brain: Their transport and utilization. Brain Res. Rev., 2006, 52, 389-397.
5. King, A. E.; Ackley, M. A.; Cass, C. E.; Young, J. D.; Baldwin, S. A. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol. Sci., 2006, 27, 416-425.
6. Sonoda, T.; Tatibana, M. Metabolic fate of pyrimidines and purines in dietary nucleic acids ingested by mice. Biochim. Biophys. Acta, 1978, 521, 55-66.
7. He, Y.; Sanderson, I. R.; Walker, W. A. Uptake, transport and metabolism of exogenous nucleosides in intestinal epithelial cell cultures. J. Nutr., 1994, 124, 1942-1949.
8. Connolly, G. P.; Duley, J. A. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol. Sci., 1999, 20, 218-225.
9. Grimble, G. K. Dietary nucleotides and gut mucosal defence. Gut, 1994, 35, S46-51.
10. Bourget, P. A.; Tremblay, G. C. Pyrimidine biosynthesis in rat brain. J. Neurochem., 1972, 19, 1617-1624.
11. Cornford, E. M.; Oldendorf, W. H. Independent blood-brain barrier transport systems for nucleic acid precursors. Biochim. Biophys. Acta, 1975, 394, 211-219.
12. Geiger, A.; Yamasaki, S. Cytdine and uridine requirement of the brain. J. Neurochem., 1956, 1, 93-100.
13. Redzic, Z. B.; Biringer, J.; Barnes, K.; Baldwin, S. A.; Al-Sarraf, H.; Nicola, P. A.; Young, J. D.; Cass, C. E.; Barrand, M. A.; Hladky, S. B. Polarized distribution of nucleoside transporters in rat brain endothelial and choroid plexus epithelial cells. J. Neurochem., 2005, 94, 1420-1426.
14. Redzic, Z. B.; Malatiali, S. A.; Grujicic, D.; Isakovic, A. J. Expression and functional activity of nucleoside transporters in human choroid plexus. Cerebrospinal Fluid Res., 2010, 7, 2.
15. Ritzel, M. W.; Yao, S. Y.; Ng, A. M.; Mackey, J. R.; Cass, C. E.; Young, J. D. 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., 1998, 15, 203-211.
16. Zhang, J.; Smith, K. M.; Tackaberry, T.; Visser, F.; Robins, M. J.; Nielsen, L. P.; Nowak, I.; Karpinski, E.; Baldwin, S. A.; Young, J. D.; Cass, C. E. Uridine binding and transportability determinants of human concentrative nucleoside transporters. Mol. Pharmacol., 2005, 68, 830-839.
17. Traut, T. W. Physiological concentrations of purines and pyrimidines. Mol. Cell. Biochem., 1994, 140, 1-22.
18. Parkinson, F. E.; Ferguson, J.; Zamzow, C. R.; Xiong, W. Gene expression for enzymes and transporters involved in regulating adenosine and inosine levels in rat forebrain neurons, astrocytes and C6 glioma cells. J. Neurosci. Res., 2006, 84, 801-808.
19. Guillen-Gomez, E.; Calbet, M.; Casado, J.; de Lecea, L.; Soriano, E.; Pastor-Anglada, M.; Burgaya, F. Distribution of CNT2 and ENT1 transcripts in rat brain: selective decrease of CNT2 mRNA in the cerebral cortex of sleep-deprived rats. J. Neurochem., 2004, 90, 883-893.
20. Nagai, K.; Nagasawa, K.; Fujimoto, S. Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes. Biochem. Biophys. Res. Commun., 2005, 334, 1343-1350.
21. Peng, L.; Huang, R.; Yu, A.C.; Fung, K. Y.; Rathbone, M. P.; Hertz, L. Nucleoside transporter expression and function in cultured mouse astrocytes. Glia, 2005, 52, 25-35.
22. Dobolyi, A.; Reichart, A.; Szikra, T.; Szilagyi, N.; Kekesi, A. K.; Karancsi, T.; Slegel, P.; Palkovits, M.; Juhasz, G. Analysis of purine and pyrimidine bases, nucleosides and deoxynucleosides in brain microsamples (microdialysates and micropunches) and cerebrospinal fluid. Neurochem. Int., 1998, 32, 247-256.
23. Dobolyi, A.; Reichart, A.; Szikra, T.; Juhasz, G. Purine and pyrimidine nucleoside content of the neuronal extracellular space in rat. An in vivo microdialysis study. Adv. Exp. Med. Biol., 1998, 431, 83-87.
24. Kekesi, K.A.; Kovacs, Z.; Szilagyi, N.; Bobest, M.; Szikra, T.; Dobolyi, A.; Juhasz, G.; Palkovits, M. Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain. Cell. Mol. Neurobiol., 2006, 26, 833-844.
25. Kovacs, Z.; Dobolyi, A.; Juhasz, G.; Kekesi, K.A. Nucleoside map of the human central nervous system. Neurochem. Res., 2010, 35, 452-464.
26. Kovacs, Z.; Juhasz, G.; Dobolyi, A.; Bobest, M.; Papp, V.; Takats, L.; Kekesi, K. A. Gender-and age-dependent changes in nucleoside levels in the cerebral cortex and white matter of the human brain. Brain Res. Bull., 2010, 81, 579-584.
27. Dobolyi, A.; Reichart, A.; Szikra, T.; Nyitrai, G.; Kekesi, K. A.; Juhasz, G. Sustained depolarisation induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus. Neurochem. Int., 2000, 37, 71-79.
28. Dobolyi, A.; Szikra, T.; Kekesi, A. K.; Kovacs, Z.; Juhasz, G. Uridine is released by depolarization and inhibits unit activity in the rat hippocampus. Neuroreport, 1999, 10, 3049-3053.
29. Slezia, A.; Kekesi, A. K.; Szikra, T.; Papp, A. M.; Nagy, K.; Szente, M.; Magloczky, Z.; Freund, T.F.; Juhasz, G. Uridine release during aminopyridine-induced epilepsy. Neurobiol. Dis., 2004, 16, 490-499.
30. Nyitrai, G.; Kekesi, K. A.; Szilagyi, N.; Papp, A.; Juhasz, G.; Kardos, J. Neurotoxicity of lindane and picrotoxin: neurochemical and electrophysiological correlates in the rat hippocampus in vivo. Neurochem. Res., 2002, 27, 139-145.
31. Balestri, F.; Barsotti, C.; Lutzemberger, L.; Camici, M.; Ipata, P. L. Key role of uridine kinase and uridine phosphorylase in the homeostatic regulation of purine and pyrimidine salvage in brain. Neurochem. Int., 2007, 51, 517-523.
32. Genchev, D. D.; Mandel, P. CTP synthetase activity in neonatal and adult rat brain. J. Neurochem., 1974, 22, 1027-1030.
33. Ross, B. M.; Moszczynska, A.; Blusztajn, J. K.; Sherwin, A.; Lozano, A.; Kish, S. J. Phospholipid biosynthetic enzymes in human brain. Lipids, 1997, 32, 351-358.
34. Vertessy, B. G.; Toth, J. Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases. Acc. Chem. Res., 2009, 42, 97-106.
35. Brown, A. M. Brain glycogen re-awakened. J. Neurochem., 2004, 89, 537-552.
36. Lecca, D.; Ceruti, S. Uracil nucleotides: From metabolic intermediates to neuroprotection and neuroinflammation. Biochem. Pharmacol., 2008, 75, 1869-1881.
37. Ipata, P. L.; Barsotti, C.; Tozzi, M. G.; Camici, M.; Balestri, F. Metabolic interplay between intra-and extra-cellular uridine metabolism via an ATP driven uridine-UTP cycle in brain. Int. J. Biochem. Cell. Biol., 2010, 42, 932-937.
38. Lazarowski, E. R. Quantification of extracellular UDP-galactose. Anal. Biochem., 2010, 396, 23-29.
39. Lazarowski, E. R.; Boucher, R. C. UTP as an extracellular signaling molecule. News Physiol. Sci., 2001, 16, 1-5.
40. Brunschweiger, A.; Muller, C.E. P2 receptors activated by uracil nucleotides--an update. Curr. Med. Chem., 2006, 13, 289-312.
41. Connolly, G. P. Abnormal pyrimidine metabolism is the basis of some neurological diseases. Trends Pharmacol. Sci., 1998, 19, 252.
42. Borbely, A. A.; Tobler, I. Endogenous sleep-promoting substances and sleep regulation. Physiol. Rev., 1989, 69, 605-670.
43. Inoue, S. Sleep and sleep substances. Brain Dev., 1986, 8, 469-473.
44. Honda, K.; Komoda, Y.; Nishida, S.; Nagasaki, H.; Higashi, A.; Uchizono, K.; Inoue, S. Uridine as an active component of sleeppromoting substance: its effects on nocturnal sleep in rats. Neurosci. Res., 1984, 1, 243-252.
45. Honda, K.; Okano, Y.; Komoda, Y.; Inoue, S. Sleep-promoting effects of intraperitoneally administered uridine in unrestrained rats. Neurosci. Lett., 1985, 62, 137-141.
46. Saper, C. B. Staying awake for dinner: hypothalamic integration of sleep, feeding, and circadian rhythms. Prog. Brain Res., 2006, 153, 243-252.
47. Kimura-Takeuchi, M.; Inoue, S. Lateral preoptic lesions void slowwave sleep enhanced by uridine but not by muramyl dipeptide in rats. Neurosci. Lett., 1993, 157, 17-20.
48. Roberts, C. A.; Kreisman, N. R.; Waltman, M. Uridine anticonvulsant effects: selective control of nucleoside incorporation in experimental epilepsy. Epilepsia, 1974, 15, 479-500.
49. Roberts, C. A. Anticonvulsant effects of uridine: comparative analysis of metrazol and penicillin induced foci. Brain Res., 1973, 55, 291-308.
50. Dwivedi, C.; Harbison, R. D. Anticonvulsant activities of delta-8 and delta-9 tetrahydrocannabinol and uridine. Toxicol. Appl. Pharmacol., 1975, 31, 452-458.
51. Piccoli, F.; Camarda, R.; Bonavita, V. The brain nucleotide pattern of the rat after injection of uracil, uridine and uridine phosphate. Acta Neurol., (Napol) 1971, 26, 109-117.
52. Zhao, Q.; Marolewski, A.; Rusche, J. R.; Holmes, G. L. Effects of uridine in models of epileptogenesis and seizures. Epilepsy Res., 2006, 70, 73-82.
53. Zhao, Q.; Shatskikh, T.; Marolewski, A.; Rusche, J. R.; Holmes, G. L. Effects of uridine on kindling. Epilepsy Behav., 2008, 13, 47-51.
54. Peters, G. J.; van Groeningen, C. J.; Laurensse, E. J.; Lankelma, J.; Leyva, A.; Pinedo, H. M. Uridine-induced hypothermia in mice and rats in relation to plasma and tissue levels of uridine and its metabolites. Cancer Chemother. Pharmacol., 1987, 20, 101-108.
55. Peters, G. J.; van Groeningen, C. J.; Laurensse, E.; Kraal, I.; Leyva, A.; Lankelma, J.; Pinedo, H. M. Effect of pyrimidine nucleosides on body temperatures of man and rabbit in relation to pharmacokinetic data. Pharm. Res., 1987, 4, 113-119.
56. Myers, C. S.; Fisher, H.; Wagner, G. C. Uridine potentiates haloperidol's disruption of conditioned avoidance responding. Brain Res., 1994, 651, 194-198.
57. Agnati, L. F.; Fuxe, K.; Ruggeri, M.; Merlo Pich, E.; Benfenati, F.; Volterra, V.; Ungerstedt, U.; Zini, I. Effects of chronic treatment with uridine on striatal dopamine release and dopamine related behaviours in the absence or the presence of chronic treatment with haloperidol. Neurochem. Int., 1989, 15, 107-113.
58. Wang, L.; Pooler, A. M.; Albrecht, M. A.; Wurtman, R. J. Dietary uridine-5'-monophosphate supplementation increases potassiumevoked dopamine release and promotes neurite outgrowth in aged rats. J. Mol. Neurosci., 2005, 27, 137-145.
59. Myers, C. S.; Napolitano, M.; Fisher, H.; Wagner, G. C. Uridine and stimulant-induced motor activity. Proc. Soc. Exp. Biol. Med., 1993, 204, 49-53.
60. Farabegoli, C.; Merlo Pich, E.; Cimino, M.; Agnati, L. F.; Fuxe, K. Chronic uridine treatment reduces the level of [3H]spiperonelabelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours. Acta Physiol. Scand., 1988, 132, 209-216.
61. Bernardini, R.; De Luca, G.; Marino, D. Effect of glutamine and nucleosides on prolactin secretion in the rat. Acta Eur. Fertil., 1983, 14, 341-344.
62. Karkishchenko, N. N.; Khaitin, M. I.; Simkina Iu, N. A pharmacological analysis of the anxiolytic activity of uridine. Farmakol. Toksikol, 1991, 54, 16-18.
63. Karkishchenko, N. N.; Makliakov Iu, S.; Stradomskii, B. V. Pyrimidine derivatives: their psychotropic properties and the molecular mechanisms of their central action. Farmakol. Toksikol, 1990, 53, 67-72.
64. Teather, L. A.; Wurtman, R. J. Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol. Psychiatry, 2003, 27, 711-717.
65. Teather, L. A.; Wurtman, R. J. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats. Learn. Mem., 2005, 12, 39-43.
66. Teather, L. A.; Wurtman, R. J. Chronic administration of UMP ameliorates the impairment of hippocampal-dependent memory in impoverished rats. J. Nutr., 2006, 136, 2834-2837.
67. Wurtman, R. J.; Regan, M.; Ulus, I.; Yu, L. Effect of oral CDPcholine on plasma choline and uridine levels in humans. Biochem. Pharmacol., 2000, 60, 989-992.
68. Holguin, S.; Martinez, J.; Chow, C.; Wurtman, R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J., 2008, 22, 3938-3946.
69. Spiers, P. A.; Myers, D.; Hochanadel, G. S.; Lieberman, H. R.; Wurtman, R. J. Citicoline improves verbal memory in aging. Arch. Neurol., 1996, 53, 441-448.
70. Pooler, A. M.; Guez, D. H.; Benedictus, R.; Wurtman, R. J. Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected]. Neuroscience, 2005, 134, 207-214.
71. Wurtman, R. J.; Ulus, I. H.; Cansev, M.; Watkins, C. J.; Wang, L.; Marzloff, G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res., 2006, 1088, 83-92.
72. Wurtman, R. J.; Cansev, M.; Ulus, I. H. Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J. Nutr. Health Aging, 2009, 13, 189-197.
73. Wurtman, R. J.; Cansev, M.; Sakamoto, T.; Ulus, I. H. Use of phosphatide precursors to promote synaptogenesis. Annu. Rev. Nutr., 2009, 29, 59-87.
74. Sakamoto, T.; Cansev, M.; Wurtman, R. J. Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res., 2007, 1182, 50-59.
75. Cansev, M.; Marzloff, G.; Sakamoto, T.; Ulus, I.H.; Wurtman, R. J. Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups. Dev. Neurosci., 2009, 31, 181-192.
76. Wurtman, R. J. Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metabol. Clin. Exp., 2008, 57, S6-S10.
77. Cansev, M.; Wurtman, R. J.; Sakamoto, T.; Ulus, I. H. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement., 2008, 4, S153-168.
78. Wurtman, R. J.; Cansev, M.; Sakamoto, T.; Ulus, I. H. Administration of docosahexaenoic acid, uridine and choline increases levels of synaptic membranes and dendritic spines in rodent brain. World Rev. Nutr. Diet, 2009, 99, 71-96.
79. Wang, L.; Albrecht, M. A.; Wurtman, R. J. Dietary supplementation with uridine-5'-monophosphate (UMP, a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat. Brain Res., 2007, 1133, 42-48.
80. Zeisel, S. H. Dietary influences on neurotransmission. Adv. Pediatr., 1986, 33, 23-47.
81. Richardson, U. I.; Watkins, C. J.; Pierre, C.; Ulus, I. H.; Wurtman, R. J. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res., 2003, 971, 161-167.
82. Cansev, M.; Watkins, C. J.; van der Beek, E. M.; Wurtman, R. J. Oral uridine-5'-monophosphate (UMP) increases brain CDPcholine levels in gerbils. Brain Res., 2005, 1058, 101-108.
83. Anderson, C. M.; Parkinson, F. E. Potential signalling roles for UTP and UDP: sources, regulation and release of uracil nucleotides. Trends Pharmacol. Sci., 1997, 18, 387-392.
84. Ogilvie, A.; Blasius, R.; Schulze-Lohoff, E.; Sterzel, R. B. Adenine dinucleotides: a novel class of signalling molecules. J. Auton. Pharmacol., 1996, 16, 325-328.
85. Pankratov, Y.; Lalo, U.; Verkhratsky, A.; North, R. A. Vesicular release of ATP at central synapses. Pflugers Arch., 2006, 452, 589-597.
86. Saiag, B.; Bodin, P.; Shacoori, V.; Catheline, M.; Rault, B.; Burnstock, G. Uptake and flow-induced release of uridine nucleotides from isolated vascular endothelial cells. Endothelium, 1995, 2, 279-275.
87. Lazarowski, E. R.; Homolya, L.; Boucher, R. C.; Harden, T. K. Direct demonstration of mechanically induced release of cellular UTP and its implication for uridine nucleotide receptor activation. J. Biol. Chem., 1997, 272, 24348-24354.
88. Lazarowski, E. R.; Harden, T. K. Quantitation of extracellular UTP using a sensitive enzymatic assay. Br. J. Pharmacol., 1999, 127, 1272-1278.
89. Elliott, M. R.; Chekeni, F. B.; Trampont, P. C.; Lazarowski, E. R.; Kadl, A.; Walk, S. F.; Park, D.; Woodson, R. I.; Ostankovich, M.; Sharma, P.; Lysiak, J. J.; Harden, T. K.; Leitinger, N.; Ravichandran, K. S. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature, 2009, 461, 282-286.
90. Tatur, S.; Kreda, S.; Lazarowski, E.; Grygorczyk, R. Calciumdependent release of adenosine and uridine nucleotides from A549 cells. Purinergic Signal., 2008, 4, 139-146.
91. 2+-dependent ATP release from A549 cells involves synergistic autocrine stimulation by coreleased uridine nucleotides. J. Physiol., 2007, 584, 419-435.
92. Harden, T. K.; Lazarowski, E. R. Release of ATP and UTP from astrocytoma cells. Prog. Brain Res., 1999, 120, 135-143.
93. Lazarowski, E. Regulated release of nucleotides and UDP sugars from astrocytoma cells. Novartis Found. Symp., 2006, 276, 73-84; discussion 84-90, 107-112, 275-181.
94. Lazarowski, E. R.; Shea, D. A.; Boucher, R. C.; Harden, T. K. Release of cellular UDP-glucose as a potential extracellular signaling molecule. Mol. Pharmacol., 2003, 63, 1190-1197.
95. Sesma, J. I.; Esther, C. R., Jr.; Kreda, S. M.; Jones, L.; O'Neal, W.; Nishihara, S.; Nicholas, R. A.; Lazarowski, E. R. Endoplasmic reticulum/ golgi nucleotide sugar transporters contribute to the cellular release of UDP-sugar signaling molecules. J. Biol. Chem., 2009, 284, 12572-12583.
96. Abbracchio, M. P.; Burnstock, G.; Verkhratsky, A.; Zimmermann, H. Purinergic signalling in the nervous system: an overview. Trends Neurosci., 2009, 32, 19-29.
97. Hussl, S.; Boehm, S. Functions of neuronal P2Y receptors. Pflugers Arch., 2006, 452, 538-551.
98. Moore, D. J.; Murdock, P. R.; Watson, J. M.; Faull, R. L.; Waldvogel, H. J.; Szekeres, P. G.; Wilson, S.; Freeman, K. B.; Emson, P. C. GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function. Brain Res. Mol. Brain Res., 2003, 118, 10-23.
99. Ciana, P.; Fumagalli, M.; Trincavelli, M. L.; Verderio, C.; Rosa, P.; Lecca, D.; Ferrario, S.; Parravicini, C.; Capra, V.; Gelosa, P.; Guerrini, U.; Belcredito, S.; Cimino, M.; Sironi, L.; Tremoli, E.; Rovati, G. E.; Martini, C.; Abbracchio, M. P. The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J., 2006, 25, 4615-4627.
100. Moore, D. J.; Chambers, J. K.; Wahlin, J. P.; Tan, K. B.; Moore, G. B.; Jenkins, O.; Emson, P. C.; Murdock, P. R. Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcriptionpolymerase chain reaction study. Biochim. Biophys. Acta, 2001, 1521, 107-119.
101. Amadio, S.; D'Ambrosi, N.; Cavaliere, F.; Murra, B.; Sancesario, G.; Bernardi, G.; Burnstock, G.; Volonte, C. P2 receptor modulation and cytotoxic function in cultured CNS neurons. Neuropharmacology, 2002, 42, 489-501.
102. Bennett, G. C.; Ford, A. P.; Smith, J. A.; Emmett, C. J.; Webb, T. E.; Boarder, M. R. P2Y receptor regulation of cultured rat cerebral cortical cells: calcium responses and mRNA expression in neurons and glia. Br. J. Pharmacol., 2003, 139, 279-288.
103. Jia, C.; Doherty, J. P.; Crudgington, S.; Hegg, C. C. Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium. Neuroscience, 2009, 163, 120-128.
104. Grimm, I.; Messemer, N.; Stanke, M.; Gachet, C.; Zimmermann, H. Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells. J. Cell. Sci., 2009, 122, 2524-2533.
105. Tian, M. L.; Zou, Z.; Yuan, H. B.; Wang, C. C.; Zhu, Q. F.; Xu, H. T.; Gao, X.; Shi, X. Y. Uridine 5'-triphosphate (UTP) protects against cerebral ischemia reperfusion injury in rats. Neurosci. Lett., 2009, 465, 55-60.
106. Inoue, K.; Koizumi, S.; Kataoka, A.; Tozaki-Saitoh, H.; Tsuda, M. P2Y(6)-Evoked Microglial Phagocytosis. Int. Rev. Neurobiol., 2009, 85, 159-163.
107. Zimmermann, H. Biochemistry, localization and functional roles of ecto-nucleotidases in the nervous system. Prog. Neurobiol., 1996, 49, 589-618.
108. Connolly, G. P.; Demaine, C.; Duley, J. A. Ecto-nucleotidases in isolated intact rat vagi, nodose ganglia, and superior cervical ganglia. Adv. Exp. Med. Biol., 1998, 431, 769-776.
109. 2+ ion fluxes in rat brain homogenates. Neuroreport, 1999, 10, 1577-1582.
110. Guarneri, P.; Guarneri, R.; Mocciaro, C.; Piccoli, F. Interaction of uridine with GABA binding sites in cerebellar membranes of the rat. Neurochem. Res., 1983, 8, 1537-1545.
111. Guarneri, P.; Guarneri, R.; La Bella, V.; Piccoli, F. Interaction between uridine and GABA-mediated inhibitory transmission: studies in vivo and in vitro. Epilepsia, 1985, 26, 666-671.
112. Yamamoto, I.; Kimura, T.; Tateoka, Y.; Watanabe, K.; Ho, I. K. Nsubstituted oxopyrimidines and nucleosides: structure-activity relationship for hypnotic activity as central nervous system depressant. J. Med. Chem., 1987, 30, 2227-2231.
113. Yamamoto, I.; Kimura, T.; Tateoka, Y.; Watanabe, K.; Ho, I.K. N3-benzyluridine exerts hypnotic activity in mice. Chem. Pharm. Bull., (Tokyo), 1985, 33, 4088-4090.
114. Kimura, T.; Watanabe, K.; Koshigami, M.; Miyamoto, K.; Kondo, S.; Yamamoto, I. The 6-azauridine analogues possessing sedative and hypnotic effects. Nucleic Acids Symp. Ser., 1992, 27, 199-200.
115. Koshigami, M.; Watanabe, K.; Kimura, T.; Yamamoto, I. Central depressant effects of N3-substituted 6-azauridines in mice. Chem. Pharm. Bull., (Tokyo, 1991, 39, 2597-2599.
116. Yamamoto, I.; Kuze, J.; Kimura, T.; Watanabe, K.; Kondo, S.; Ho, I.K. The potent depressant effects of N3-phenacyluridine in mice. Biol. Pharm. Bull., 1994, 17, 514-516.
117. Kimura, T.; Miki, M.; Ikeda, M.; Yonemoto, S.; Watanabe, K.; Kondo, S.; Ho, I. K.; Yamamoto, I. Possible existence of a novel receptor for uridine analogues in the central nervous system using two isomers, N3-(S)-(+)-and N3-(R)-(-)-alpha-hydroxy-betaphenethyluridines. Biol. Pharm. Bull., 2001, 24, 729-731.
118. Kimura, T.; Miki, M.; Watanabe, K.; Kondo, S.; Ho, I. K.; Yamamoto, I. Binding affinity of N3-substituted uridine for synaptic membrane and their CNS depressant effects. Nucleic Acids Symp. Ser., 1995, 34, 147-148.
119. Kimura, T.; Ho, I. K.; Yamamoto, I. Uridine receptor: discovery and its involvement in sleep mechanism. Sleep, 2001, 24, 251-260.
120. Kovacs, I.; Lasztoczi, B.; Szarics, E.; Heja, L.; Sagi, G.; Kardos, J. Characterisation of an uridine-specific binding site in rat cerebrocortical homogenates. Neurochem. Int., 2003, 43, 101-112.
121. Wong, L. A.; Mayer, M. L.; Jane, D. E.; Watkins, J. C. Willardiines differentiate agonist binding sites for kainate-versus AMPApreferring glutamate receptors in DRG and hippocampal neurons. J. Neurosci., 1994, 14, 3881-3897.
122. Ashworth, T. S.; Brown, E. G.; Roberts, F. M. Biosynthesis of willardiine and isowillardiine in germinating pea seeds and seedlings. Biochem. J., 1972, 129, 897-905.
123. Gorodinsky, A.; Paas, Y.; Teichberg, V.I. A ligand binding study of the interactions of guanine nucleotides with non-NMDA receptors. Neurochem. Int., 1993, 23, 285-291.
124. Paas, Y.; Devillers-Thiery, A.; Changeux, J.P.; Medevielle, F.; Teichberg, V. I. Identification of an extracellular motif involved in the binding of guanine nucleotides by a glutamate receptor. EMBO J., 1996, 15, 1548-1556.
125. van Groeningen, C. J.; Peters, G. J.; Pinedo, H. M. Reversal of 5-fluorouracil-induced toxicity by oral administration of uridine. Ann. Oncol., 1993, 4, 317-320.
126. van Groeningen, C. J.; Peters, G. J.; Nadal, J. C.; Laurensse, E.; Pinedo, H.M. Clinical and pharmacologic study of orally administered uridine. J. Natl. Cancer Inst., 1991, 83, 437-441.
127. van Groeningen, C. J.; Peters, G. J.; Pinedo, H. M. Modulation of fluorouracil toxicity with uridine. Semin. Oncol., 1992, 19, 148-154.
128. Page, T.; Yu, A.; Fontanesi, J.; Nyhan, W. L. Developmental disorder associated with increased cellular nucleotidase activity. Proc. Natl. Acad. Sci. USA, 1997, 94, 11601-11606.
129. van der Beek, E. M.; Kamphuis, P. The potential role of nutritional components in the management of Alzheimer's Disease. Eur. J. Pharmacol., 2008, 585, 197-207.
130. Cerpa, W.; Dinamarca, M. C.; Inestrosa, N. C. Structure-function implications in Alzheimer's disease: effect of Abeta oligomers at central synapses. Curr. Alzheimer Res., 2008, 5, 233-243.
131. Kamphuis, P. J.; Wurtman, R. J. Nutrition and Alzheimer's disease: pre-clinical concepts. Eur. J. Neurol., 2009, 16, 12-18.
132. Cansev, M.; Ulus, I. H.; Wang, L.; Maher, T. J.; Wurtman, R. J. Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson's disease. Neurosci. Res., 2008, 62, 206-209.