Physiological roles of vascular nucleoside transporters

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 27, Issue 5, 2007, Pages 1004-1013

  Löffler, Michaela ^a   Morote Garcia, Julio C ^a   Eltzschig, Shelley A ^a   Coe, Imogen R ^b   Eltzschig, Holger K ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b YORK UNIVERSITY   (Canada)

Author keywords

Adenosine signaling; Concentrative nucleoside transporter; Endothelial barrier; Equilibrative nucleoside transporter; Hypoxia; Inflammation; Ischemia; Preconditioning

Indexed keywords

ADENOSINE; DILAZEP; DIPYRIDAMOLE; DRAFLAZINE; HYPOXIA INDUCIBLE FACTOR 1; NUCLEOSIDE TRANSPORTER; TROGLITAZONE;

AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CORONARY ARTERY DILATATION; HUMAN; HYPOXIA; INFLAMMATION; ISCHEMIC PRECONDITIONING; NONHUMAN; NUCLEOTIDE METABOLISM; PASSIVE TRANSPORT; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; SHORT SURVEY; SIGNAL TRANSDUCTION; THROMBOCYTE AGGREGATION;

ADENOSINE; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD VESSELS; ENDOTHELIUM, VASCULAR; HUMANS; NUCLEOSIDE TRANSPORT PROTEINS; VASODILATION;

EID: 34247334945     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.106.126714     Document Type: Short Survey

References (112)

1. King AE, Ackley MA, Cass CE, Young JD, Baldwin SA. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci. 2006;27:416.
2. Hyde RJ, Cass CE, Young JD, Baldwin SA. 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. 2001;18:53-63.
3. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. 2004;447:735-743.
4. Gray JH, Owen RP, Giacomini KM. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 2004;447:728-734.
5. Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 2001;414:916-920.
6. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, Ohta A, Thiel M. Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Ann Rev Immunol. 2004;22:657-682.
7. Eltzschig HK, Eckle T, Mager A, Kuper N, Karcher C, Weissmuller T, Boengler K, Schulz R, Robson SC, Colgan SP. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res. 2006.
8. Linden J. Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol. 2001;41:775-787.
9. Kukulski F, Levesque SA, Lavoie EG, Lecka J, Bigonnesse F, Knowles AF, Robson SC, Kirley TL, Sevigny J. Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8. Purinergic Signaling. 2005;1:193-204.
10. Robson SC, Sevigny J, Zimmermann H. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signaling. 2006;2:409-430.
11. Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP. Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med. 2004;200:1395-1405.
12. Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK, Hansen KR, Thompson LF, Colgan SP. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest. 2002;110:993-1002.
13. Eltzschig HK, Ibla JC, Furuta GT, Leonard MO, Jacobson KA, Enjyoji K, Robson SC, Colgan SP. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J Exp Med. 2003;198:783-796.
14. Lennon PF, Taylor CT, Stahl GL, Colgan SP. Neutrophil-derived 5′-Adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation. J Exp Med. 1998;188:1433-1443.
15. Eltzschig HK, Abdulla P, Hoffman E, Hamilton KE, Daniels D, Schonfeld C, Loffler M, Reyes G, Duszenko M, Karhausen J, Robinson A, Westerman KA, Coe IR, Colgan SP. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J Exp Med. 2005;202:1493-1505.
16. Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114:1098-1106.
17. Karhausen J, Haase VH, Colgan SP, Davies S, Collins P, Wang D, Sigwart U, Pepper J. Inflammatory hypoxia: role of hypoxia-inducible factor. Cell Cycle. 2005;4:256-258.
18. Eltzschig HK, Thompson LF, Karhausen J, Cotta RJ, Ibla JC, Robson SC, Colgan SP. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood. 2004;104:3986-3992.
19. Sitkovsky M, Lukashev D. Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol. 2005;5:712-721.
20. Thiel M, Chouker A, Ohta A, Jackson E, Caldwell C, Smith P, Lukashev D, Bittmann I, Sitkovsky MV. Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury. PLoS Biol. 2005;3:e174.
21. Costa F, Sulur P, Angel M, Cavalcante J, Haile V, Christman B, Biaggioni I. Intravascular source of adenosine during forearm ischemia in humans: implications for reactive hyperemia. Hypertension. 1999;33:1453-1457.
22. MacLean DA, Sinoway LI, Leuenberger U. Systemic hypoxia elevates skeletal muscle interstitial adenosine levels in humans. Circulation. 1998;98:1990-1992.
23. Saito H, Nishimura M, Shinano H, Makita H, Tsujino I, Shibuya E, Sato F, Miyamoto K, Kawakami Y. Plasma concentration of adenosine during normoxia and moderate hypoxia in humans. Am J Respir Crit Care Med. 1999;159:1014-1018.
24. Phillis JW, O'Regan MH, Perkins LM. Measurement of rat plasma adenosine levels during normoxia and hypoxia. Life Sci. 1992;51:PL149-P152.
25. Mo FM, Ballard HJ. The effect of systemic hypoxia on interstitial and blood adenosine, AMP, ADP and ATP in dog skeletal muscle. J Physiol (Lond). 2001;536:593-603.
26. Kong W, Engel K, Wang J. Mammalian nucleoside transporters. Curr Drug Metab. 2004;5:63-84.
27. Eckle T, Grenz A, Kohler D, Redel A, Falk M, Rolauffs B, Osswald H, Kehl F, Eltzschig HK. Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. Am J Physiol Heart Circ Physiol. 2006;291:H2533-H2540.
28. Miura T, Ogawa T, Iwamoto T, Shimamoto K, Iimura O. Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic pre-conditioning. Circulation. 1992;86:979-985.
29. Baldwin SA, Mackey JR, Cass CE, Young JD. Nucleoside transporters: molecular biology and implications for therapeutic development. Mol Med Today. 1999;5:216-224.
30. Visser F, Vickers MF, Ng AM, Baldwin SA, Young JD, Cass CE. 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. 2002;277:395-401.
31. Sundaram M, Yao SY, Ingram JC, Berry ZA, Abidi F, Cass CE, Baldwin SA, Young JD. 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. 2001;276:45270-45275.
32. Sundaram M, Yao SY, Ng AM, Cass CE, Baldwin SA, Young JD. Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins. Biochemistry. 2001;40:8146-8151.
33. Sundaram M, Yao SY, Ng AM, Griffiths M, Cass CE, Baldwin SA, Young JD. Chimeric constructs between human and rat equilibrative nucleoside transporters (hENT1 and rENT1) reveal hENT1 structural domains interacting with coronary vasoactive drugs. J Biol Chem. 1998;273:21519-21525.
34. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD. 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. 2001;18:161-167.
35. Yao SY, Ng AM, Vickers MF, Sundaram M, Cass CE, Baldwin SA, Young JD. 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. 2002;277:24938-24948.
36. Coe IR, Griffiths M, Young JD, Baldwin SA, Cass CE. Assignment of the human equilibrative nucleoside transporter (hENT1) to 6p21.1-p21.2. Genomics. 1997;45:459-460.
37. Griffith DA, Jarvis SM. Nucleoside and nucleobase transport systems of mammalian cells. Biochim Biophys Acta. 1996;1286:153-181.
38. Griffiths M, Beaumont N, Yao SY, Sundaram M, Boumah CE, Davies A, Kwong FY, Coe I, Cass CE, Young JD, Baldwin SA. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat Med. 1997;3:89-93.
39. Hamilton SR, Yao SY, Ingram JC, Hadden DA, Ritzel MW, Gallagher MP, Henderson PJ, Cass CE, Young JD, Baldwin SA. Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1. J Biol Chem. 2001;276:27981-27988.
40. Archer RG, Pitelka V, Hammond JR. Nucleoside transporter subtype expression and function in rat skeletal muscle microvascular endothelial cells. Br J Pharmacol. 2004;143:202-214.
41. Choi DS, Cascini MG, Mailliard W, Young H, Paredes P, McMahon T, Diamond I, Bonci A, Messing RO. The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference. Nat Neurosci. 2004.
42. Aymerich I, Duflot S, Fernandez-Veledo S, Guillen-Gomez E, Huber-Ruano I, Casado FJ, Pastor-Anglada M. The concentrative nucleoside transporter family (SLC28): new roles beyond salvage? Biochem Soc Trans. 2005;33:216-219.
43. Podgorska M, Kocbuch K, Pawelczyk T. Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters. Acta Biochim Pol. 2005;52:749-758.
44. Crawford CR, Patel DH, Naeve C, Belt JA. Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line. J Biol Chem. 1998;273:5288-5293.
45. Griffiths M, Yao SY, Abidi F, Phillips SE, Cass CE, Young JD, Baldwin SA. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem J. 1997;328(Pt 3):739-743.
46. Ward JL, Sherali A, Mo ZP, Tse CM. 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. 2000;275:8375-8381.
47. Baldwin SA, Yao SY, Hyde RJ, Ng AM, Foppolo S, Barnes K, Ritzel MW, Cass CE, Young JD. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem. 2005;280:15880-15887.
48. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel MW, Claycomb WC, Cass CE, Young JD, Billeter-Clark R, Boyett MR, Baldwin SA. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res. 2006;99:510-519.
49. Chishty M, Begley DJ, Abbott NJ, Reichel A. Functional characterisation of nucleoside transport in rat brain endothelial cells. Neuroreport. 2003;14:1087-1090.
50. 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. 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. 2001;276:2914-2927.
51. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol. 1997;272:C707-714.
52. Ritzel MW, Yao SY, Ng AM, Mackey JR, Cass CE, Young JD. 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.
53. del Santo B, Valdes R, Mata J, Felipe A, Casado FJ, Pastor-Anglada M. Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells. Hepatology. 1998;28:1504-1511.
54. Anderson CM, Xiong W, Young JD, Cass CE, Parkinson FE. Demonstration of the existence of mRNAs encoding N1/cif and N2/cit sodium/nucleoside cotransporters in rat brain. Brain Res Mol Brain Res. 1996;42:358-361.
55. Wang J, Schaner ME, Thomassen S, Su SF, Piquette-Miller M, Giacomini KM. Functional and molecular characteristics of Na(+)-dependent nucleoside transporters. Pharm Res. 1997;14:1524-1532.
56. del Santo B, Tarafa G, Felipe A, Casado FJ, Pastor-Anglada M. Developmental regulation of the concentrative nucleoside transporters CNT1 and CNT2 in rat liver. J Hepatol. 2001;34:873-880.
57. Dragan Y, Valdes R, Gomez-Angelats M, Felipe A, Javier Casado F, Pitot H, Pastor-Anglada M. Selective loss of nucleoside carrier expression in rat hepatocarcinomas. Hepatology. 2000;32:239-246.
58. Soler C, Valdes R, Garcia-Manteiga J, Xaus J, Comalada M, Casado FJ, Modolell M, Nicholson B, MacLeod C, Felipe A, Celada A, Pastor-Anglada M. 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. J Biol Chem. 2001;276:30043-30049.
59. Soler C, Garcia-Manteiga J, Valdes R, Xaus J, Comalada M, Casado FJ, Pastor-Anglada M, Celada A, Felipe A. Macrophages require different nucleoside transport systems for proliferation and activation. Faseb J. 2001;15:1979-1988.
60. Podgorska M, Kocbuch K, Grden M, Szutowicz A, Pawelczyk T. Prevalence of unidirectional Na(+)-dependent adenosine transport and altered potential for adenosine generation in diabetic cardiac myocytes. Basic Res Cardiol. 2006;101:214-222.
61. Pennycooke M, Chaudary N, Shuralyova I, Zhang Y, Coe IR. Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem Biophys Res Commun. 2001;280:951-959.
62. Fernandez-Veledo S, Valdes R, Wallenius V, Casado FJ, Pastor-Anglada M. Up-regulation of the high-affinity pyrimidine-preferring nucleoside transporter concentrative nucleoside transporter 1 by tumor necrosis factor-alpha and interleukin-6 in liver parenchymal cells. J Hepatol. 2004;41:538-544.
63. Fernandez-Veledo S, Huber-Ruano I, Aymerich I, Duflot S, Casado FJ, Pastor-Anglada M. Bile acids alter the subcellular localization of CNT2 and increase CNT2-related transport activity in liver parenchymal cells. Biochem J. 2006.
64. Fotoohi AK, Lindqvist M, Peterson C, Albertioni F. 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. 2006;343:208-215.
65. Tamura DY, Moore EE, Partrick DA, Johnson JL, Offner PJ, Silliman CC. Acute hypoxemia in humans enhances the neutrophil inflammatory response. Shock. 2002;17:269-273.
66. Luscinskas FW, Ma S, Nusrat A, Parkos CA, Shaw SK. Leukocyte transendothelial migration: a junctional affair. Semin Immunol. 2002;14:105-113.
67. Parkos CA, Delp C, Arnaout MA, Madara JL. Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction. J Clin Invest. 1991;88:1605-1612.
68. Madara JL. Regulation of the movement of solutes across tight junctions. Annu Rev Physiol. 1998;60:143-159.
69. Luscinskas FW, Ma S, Nusrat A, Parkos CA, Shaw SK. The role of endothelial cell lateral junctions during leukocyte trafficking. Immunol Rev. 2002;186:57-67.
70. Carpenter TC, Stenmark KR. Hypoxia decreases lung neprilysin expression and increases pulmonary vascular leak. Am J Physiol Lung Cell Mol Physiol. 2001;281:L941-L948.
71. Schoch HJ, Fischer S, Marti HH. Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain. Brain. 2002;125:2549-2557.
72. Baxter GF. Role of adenosine in delayed preconditioning of myocardium. Cardiovasc Res. 2002;55:483-494.
73. Mubagwa K, Flameng W. Adenosine, adenosine receptors and myocardial protection: an updated overview. Cardiovasc Res. 2001;52:25-39.
74. Friedman GB, Taylor CT, Parkos CA, Colgan SP. Epithelial permeability induced by neutrophil transmigration is potentiated by hypoxia: role of intracellular cAMP. J Cell Physiol. 1998;176:76-84.
75. Eltzschig HK, Faigle M, Knapp S, Karhausen J, Ibla J, Rosenberger P, Odegard KC, Laussen PC, Thompson LF, Colgan SP. Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood. 2006;108:1602-1610.
76. Chaudary N, Naydenova Z, Shuralyova I, Coe IR. Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line, HL-1. Cardiovasc Res. 2004;61:780-788.
77. 76a.Casanello P, Torres A, Sanhueza F, Gonzalez M, Farias M, Gallardo V, Pastor-Anglada M, San Martin R, Sobrevia L. Equilibrative nucleoside transporter 1 expression is downregulated by hypoxia in human umbilical vein endothelium. Circ Res. 2005;97:16-24.
78. Huang LE, Gu J, Schau M, Bunn HF. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1998;95:7987-7992.
79. Cummins EP, Taylor CT. Hypoxia-responsive transcription factors. Pflugers Arch. 2005;450:363-371.
80. Leonard MO, Cottell DC, Godson C, Brady HR, Taylor CT. The role of HIF-1 alpha in transcriptional regulation of the proximal tubular epithelial cell response to hypoxia. J Biol Chem. 2003;278:40296-40304.
81. Manalo DJ, Rowan A, Lavoie T, Natarajan L, Kelly BD, Ye SQ, Garcia JG, Semenza GL. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood. 2005;105:659-669.
82. Blackburn MR. Too much of a good thing: adenosine overload in adenosine-deaminase-deficient mice. Trends Pharmacol Sci. 2003;24:66-70.
83. Driver AG, Kukoly CA, Ali S, Mustafa SJ. Adenosine in bronchoalveolar lavage fluid in asthma. Am Rev Respir Dis. 1993;148:91-97.
84. Huszar E, Vass G, Vizi E, Csoma Z, Barat E, Molnar Vilagos G, Herjavecz I, Horvath I. Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur Respir J. 2002;20:1393-1398.
85. Fozard JR, Hannon JP. Adenosine receptor ligands: potential as therapeutic agents in asthma and COPD. Pulm Pharmacol Ther. 1999;12:111-114.
86. Sun CX, Zhong H, Mohsenin A, Morschl E, Chunn JL, Molina JG, Belardinelli L, Zeng D, Blackburn MR. Role of A(2B) adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury. J Clin Invest. 2006.
87. Feoktistov I, Ryzhov S, Zhong H, Goldstein AE, Matafonov A, Zeng D, Biaggioni I. Hypoxia modulates adenosine receptors in human endothelial and smooth muscle cells toward an A2B angiogenic phenotype. Hypertension. 2004;44:649-654.
88. Eltzschig HK, Eckle T, Mager A, Kuper N, Karcher C, Weissmuller T, Boengler K, Schulz R, Robson SC, Colgan SP. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res. 2006;99:1100-1108.
89. Weissmuller T, Eltzschig HK, Colgan SP. Dynamic purine signaling and metabolism during neutrophil-endothelial interactions. Purinergic Signalling. 2005;1:229-239.
90. Kong T, Westerman KA, Faigle M, Eltzschig HK, Colgan SP. HIF-dependent induction of adenosine A2B receptor in hypoxia. Faseb J. 2006;20:2242-2250.
91. Colgan SP, Eltzschig HK, Eckle T, Thompson LF. Physiological Roles of 5′-Ectonucleotidase (CD73). Purinergic Signalling. 2006;2:351-360.
92. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124-1136.
93. Kitakaze M, Hori M, Morioka T, Minamino T, Takashima S, Sato H, Shinozaki Y, Chujo M, Mori H, Inoue M, et al. Infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of 5′-nucleotidase activity and attenuation of adenosine release. Circulation. 1994;89:1237-1246.
94. Eckle T, Krahn T, Grenz A, Köhler D, Mittelbronn M, Ledent C, Jacobson MA, Osswald H, Thompson LF, Unertl K, Eltzschig HK. Cardioprotection by ecto-5′-nucleotidase (CD73) and A2B adenosine receptors. Circulation. 2007;in press.
95. Gray J, Owen R, Giacomini K. The concentrative nucleoside transporter family, SLC28. Pfluegers Archiv Eur J Physiol. 2004;447:728.
96. Chaudary N, Naydenova Z, Shuralyova I, Coe IR. The adenosine transporter, mENT1, is a target for adenosine receptor signaling and PKC{epsilon} in hypoxic and pharmacological preconditioning in the mouse cardiomyocyte cell line, HL-1. J Pharmacol Exp Ther. 2004;jpet.104.067157.
97. Zatta AJ, Matherne GP, Headrick JP. Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart. Life Sci. 2006;78:2426-2437.
98. Leung GP, Man RY, Tse CM. Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells. Biochem Pharmacol. 2005;70:355-362.
99. Belardinelli L, Shryock JC, Snowdy S, Zhang Y, Monopoli A, Lozza G, Ongini E, Olsson RA, Dennis DM. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther. 1998;284:1066-1073.
100. Desai A, Victor-Vega C, Gadangi S, Montesinos MC, Chu CC, Cronstein BN. Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1. Mol Pharmacol. 2005;67:1406-1413.
101. Morrison RR, Talukder MA, Ledent C, Mustafa SJ. Cardiac effects of adenosine in A(2A) receptor knockout hearts: uncovering A(2B) receptors. Am J Physiol Heart Circ Physiol. 2002;282:H437-H444.
102. Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M. Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature. 1997;388:674-678.
103. Birk AV, Broekman MJ, Gladek EM, Robertson HD, Drosopoulos JH, Marcus AJ, Szeto HH. Role of extracellular ATP metabolism in regulation of platelet reactivity. J Lab Clin Med. 2002;140:166-175.
104. Strater N. Ecto-5′-Nucleotidase: Structure function relationships. Purinergic Signaling. 2006;2:343-500.
105. Robson SC, Wu Y, Sun X, Knosalla C, Dwyer K, Enjyoji K. Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in transplantation. Semin Thromb Hemost. 2005;31:217-233.
106. Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH. Loss of ATP diphosphohydrolase activity with endothelial cell activation. J Exp Med. 1997;185:153-163.
107. Luthje J. Extracellular adenine compounds, red blood cells and haemostasis: facts and hypotheses. Blut. 1989;59:367-374.
108. Sicari R, Cortigiani L, Bigi R, Landi P, Raciti M, Picano E. Prognostic value of pharmacological stress echocardiography is affected by concomitant antiischemic therapy at the time of testing. Circulation. 2004;109:2428-2431.
109. Hegedus K, Keresztes T, Fekete I, Molnar L. Effect of i.v. dipyridamole on cerebral blood flow, blood pressure, plasma adenosine and cAMP levels in rabbits. J Neurol Sci. 1997;148:153-161.
110. Snoeck E, Ver Donck K, Jacqmin P, Van Belle H, Dupont AG, Van Peer A, Danhof M. Physiological red blood cell kinetic model to explain the apparent discrepancy between adenosine breakdown inhibition and nucleoside transporter occupancy of draflazine. J Pharmacol Exp Ther. 1998;286:142-149.
111. Boleti H, Coe IR, Baldwin SA, Young JD, Cass CE. Molecular identification of the equilibrative NBMPR-sensitive (es) nucleoside transporter and demonstration of an equilibrative NBMPR-insensitive (ei) transport activity in human erythroleukemia (K562) cells. Neuropharmacology. 1997;36:1167-1179.
112. Huang M, Wang Y, Collins M, Gu JJ, Mitchell BS, Graves LM. Inhibition of nucleoside transport by p38 MAPK inhibitors. J Biol Chem. 2002;277:28364-28367.