SEARCH

SEARCH BY CITATION

Acknowledgements

The authors would like to thank P. Nickolas Shepel for performing HPLC analysis. This work was supported by the Medical Research Council (MRC) of Canada. F.E.P. is an MRC/RPP Investigator. C.J.D.S. is the recipient of a studentship award from the Manitoba Health Research Council and the Natural Sciences and Engineering Research Council of Canada. C.G.L. is the recipient of an MRC/PMAC student stipend.

  • 1
    Anderson C.M., Baldwin S.A., Young J.D., Cass C.E., Parkinson F.E. (1999a) Distribution of mRNA encoding a nitrobenzylthioinosine-insensitive nucleoside transporter (ENT2) in rat brain.Brain Res. Mol. Brain Res. 70 293297.
  • 2
    Anderson C.M., Xiong W., Geiger J.D., Young J.D., Cass C.E., Baldwin S.A., Parkinson F.E. (1999b) Distribution of equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporters (ENT1) in brain.J. Neurochem. 73 867873.
  • 3
    Ballarin M., Fredholm B.B., Ambrosio S., Mahy N. (1991) Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism.Acta Physiol. Scand. 142 97103.
  • 4
    Ballerini P., Ciccarelli R., Di Iorio P., Giuliani P., Caciagli F. (1995) Influence of Ca2+ channel modulators on [3H]purine release from rat cultured glial cells. Neurochem. Res. 20 697704.
  • 5
    Barankiewicz J., Ronlov G., Jimenez R., Gruber H.E. (1990) Selective adenosine release from human B but not T lymphoid cell line.J. Biol. Chem. 265 1573815743.
  • 6
    Barros L.F. (1994) Hypoxanthine transport in the guinea pig and human placenta is a carrier-mediated process that does not involve nucleoside transporters.Am. J. Obstet. Gynecol. 171 111117.
  • 7
    Bender A.S. & Hertz L. (1986) Similarities of adenosine uptake systems in astrocytes and neurons in primary cultures.Neurochem. Res. 11 15071524.
  • 8
    Bender A.S. & Hertz L. (1987) Dissimilarities between benzodiazepine-binding sites and adenosine uptake sites in astrocytes and neurons in primary cultures.J. Neurosci. Res. 17 154161.
  • 9
    Borgland S.L. & Parkinson F.E. (1997) Uptake and release of [3H]formycin B via sodium-dependent nucleoside transporters in mouse leukemic L1210/MA27.1 cells. J. Pharmacol. Exp. Ther. 281 347353.
  • 10
    Bradford M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding.Anal. Biochem. 72 248254.
  • 11
    Caciagli F., Ciccarelli R., Di Iorio P., Tacconelli L., Ballerini P. (1989) Influence of PLA2-PG system on purine release and cAMP content in dissociated primary glial cultures from rat striatum.Pharmacol. Res. 21 271284.
  • 12
    Caciagli F., Di Iorio P., Giuliani G., Patricelli P., Glasky A.J., Rathbone M.P., Ciccarelli R. (1999) The hypoxanthine analog AIT-082 mimics the activity of guanosine in affecting extracellular adenosine breakdown and glutamate reuptake in rat cultured astrocytes.Soc. Neurosci. Abstr. 25 1195.
  • 13
    Cass C.E., Young J.D., Baldwin S.A. (1998) Recent advances in the molecular biology of nucleoside transporters of mammalian cells.Biochem. Cell. Biol. 76 761770.
  • 14
    Ciccarelli R., Di Iorio P., Ballerini P., Ambrosini G., Giuliani P., Tiboni G.M., Caciagli F. (1994) Effects of exogenous ATP and related analogues on the proliferation rate of dissociated primary cultures of rat astrocytes.J. Neurosci. Res. 39 556566.
  • 15
    Ciccarelli R., Di Iorio P., Giuliani P., D'Alimonte I., Ballerini P., Caciagli F., Rathbone M.P. (1999) Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/hypoglycemia.Glia 25 9398.
  • 16
    Cotrina M.L., Lin J.H., Alves-Rodrigues A., Liu S., Li J., Azmi-Ghadimi H., Kang J., Naus C.C., Nedergaard M. (1998) Connexins regulate calcium signaling by controlling ATP release.Proc. Natl. Acad. Sci. USA 95 1573515740.
  • 17
    Crawford C.R., Patel D.H., Naeve C., Belt J.A. (1998) Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line.J. Biol. Chem. 273 52885293.
  • 18
    Daval J.L., Barberis C., Gayet J. (1980) Release of [14C]adenosine derivatives from superfused synaptosome preparations. Effects of depolarizing agents and metabolic inhibitors. Brain Res. 181 161174.
  • 19
    Fishbein W.N., Davis J.I., Winkert J.W., Strong D.M. (1981) Levels of adenosine deaminase, AMP deaminase, and adenylate kinase in cultured human lymphoblast lines: exquisite sensitivity of AMP deaminase to adenosine deaminase inhibitors.Biochem. Med. 26 377386.
  • 20
    Fredholm B.B. (1997) Adenosine and neuroprotection.Int. Rev. Neurobiol. 40 259280.
  • 21
    Geiger J.D., Johnston M.E., Yago V. (1988) Pharmacological characterization of rapidly accumulated adenosine by dissociated brain cells from adult rat.J. Neurochem. 51 283291.
  • 22
    Geiger J.D., Parkinson F.E., Kowaluk E.A. (1997) Regulators of endogenous adenosine levels as therapeutic targets, inPurinergic Approaches in Experimental Therapeutics (Jacobson K. A. and Jarvis M. F., eds), pp. 5584. Wiley-Liss, New York.
  • 23
    Griffith D.A. & Jarvis S.M. (1996) Nucleoside and nucleobase transport systems of mammalian cells.Biochim. Biophys. Acta 1286 153181.
  • 24
    Griffiths M., Beaumont N., Yao S.Y., Sundaram M., Boumah C.E., Davies A., Kwong F.Y., Coe I., Cass C.E., Young J.D., Baldwin S.A. (1997a) Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs.Nat. Med. 3 8993.
  • 25
    Griffiths M., Yao S.Y., Abidi F., Phillips S.E., Cass C.E., Young J.D., Baldwin S.A. (1997b) Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta.Biochem. J. 328 739743.
  • 26
    Gu J.G., Foga I.O., Parkinson F.E., Geiger J.D. (1995) Involvement of bidirectional adenosine transporters in the release of L-[3H]adenosine from rat brain synaptosomal preparations. J. Neurochem. 64 21052110.
  • 27
    Gu J.G., Nath A., Geiger J.D. (1996) Characterization of inhibitor-sensitive and -resistant adenosine transporters in cultured human fetal astrocytes.J. Neurochem. 67 972977.
  • 28
    Guthrie P.B., Knappenberger J., Segal M., Bennett M.V.L., Charles A.C., Kater S.B. (1999) ATP released from astrocytes mediates glial calcium waves.J. Neurosci. 19 520528.
  • 29
    Haun S.E., Segeleon J.E., Trapp V.L., Clotz M.A., Horrocks L.A. (1996) Inosine mediates the protective effect of adenosine in rat astrocyte cultures subjected to combined glucose-oxygen deprivation.J. Neurochem. 67 20512059.
  • 30
    Hertz L. (1978) Kinetics of adenosine uptake into astrocytes.J. Neurochem. 31 5562.
  • 31
    Hosli E. & Hosli L. (1988) Autoradiographic studies on the uptake of adenosine and on binding of adenosine analogues in neurons and astrocytes of cultured rat cerebellum and spinal cord.Neuroscience 24 621628.
  • 32
    Johnston M.E. & Geiger J.D. (1990) Adenosine transport systems on dissociated brain cells from mouse, guinea-pig, and rat.Neurochem. Res. 15 911915.
  • 33
    Jurkowitz M.S., Litsky M.L., Browning M.J., Hohl C.M. (1998) Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: correlation between protection and ATP preservation.J. Neurochem. 71 535548.
  • 34
    Lee C.W. & Jarvis S.M. (1988) Nucleoside transport in rat cerebral-cortical synaptosomes. Evidence for two types of nucleoside transporters.Biochem. J. 249 557564.
  • 35
    Litsky M.L., Hohl C.M., Lucas J.H., Jurkowitz M.S. (1999) Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia.Brain Res. 821 426432.
  • 36
    Martinek R.G. (1963) Micromethod for estimation of serum adenosine deaminase.Clin. Chem. 9 620625.
  • 37
    Matz H. & Hertz L. (1990) Effects of adenosine deaminase inhibition on active uptake and metabolism of adenosine in astrocytes in primary cultures.Brain Res. 515 168172.
  • 38
    Meghji P., Tuttle J.B., Rubio R. (1989) Adenosine formation and release by embryonic chick neurons and glia in cell culture.J. Neurochem. 53 18521860.
  • 39
    Morris P. & Montgomery J. (1998) Inhibitors of the enzyme purine nucleoside phosphorylase.Exp. Opin. Ther. Patents 8 283299.
  • 40
    Myers K.M., Fiskum G., Liu Y., Simmens S.J., Bredesen D.E., Murphy A.N. (1995) Bcl-2 protects neural cells from cyanide/aglycemia-induced lipid oxidation, mitochondrial injury, and loss of viability.J. Neurochem. 65 24322440.
  • 41
    Ogata T., Nakamura Y., Tsuji K., Shibata T., Kataoka K. (1995) A possible mechanism for the hypoxia-hypoglycemia-induced release of excitatory amino acids from cultured hippocampal astrocytes.Neurochem. Res. 20 737743.
  • 42
    Ohkubo T., Mitsumoto Y., Mohri T. (1991) Characterization of the uptake of adenosine by cultured rat hippocampal cells and inhibition of the uptake by xanthine derivatives.Neurosci. Lett. 133 275278.
  • 43
    Padua R., Geiger J.D., Dambock S., Nagy J.I. (1990) 2′-Deoxycoformycin inhibition of adenosine deaminase in rat brain:in vivo andin vitro analysis of specificity, potency, and enzyme recovery.J. Neurochem. 54 11691178.
  • 44
    Parkinson F.E., Zhang Y.W., Shepel P.N., Greenway S.C., Peeling J., Geiger J.D. (2000) Effects of nitrobenzylthioinosine on neuronal injury, adenosine levels, and adenosine receptor activity in rat forebrain ischemia.J. Neurochem. 75 795802.
  • 45
    Quaife R.A., Kohmoto O., Barry W.H. (1991) Mechanisms of reoxygenation injury in cultured ventricular myocytes.Circulation 83 566577.
  • 46
    Reyes J.L., Melendez E., Suarez J., Rangel M., Franco M., Martinez F. (1995) Modulation of the release of adenosine by glucose and chemical hypoxia in cultured renal cells (MDCK line).Biochem. Biophys. Res. Commun. 208 970977.
  • 47
    Ropp P.A. & Traut T.W. (1991) Purine nucleoside phosphorylase. Allosteric regulation of a dissociating enzyme.J. Biol. Chem. 266 76827687.
  • 48
    Rudolphi K.A., Schubert P., Parkinson F.E., Fredholm B.B. (1992) Neuroprotective role of adenosine in cerebral ischaemia.Trends Pharmacol. Sci. 13 439445.
  • 49
    Schrader J. & Gerlach E. (1976) Compartmentation of cardiac adenine nucleotides and formation of adenosine.Pflugers Arch. 367 129135.
  • 50
    Schubert P., Rudolphi K.A., Fredholm B.B., Nakamura Y. (1994) Modulation of nerve and glial function by adenosine—role in the development of ischemic damage. Int. J. Biochem. 26 12271236.
  • 51
    Shank R.P. & Baldy W.J. (1990) Adenosine transport by rat and guinea pig synaptosomes: basis for differential sensitivity to transport inhibitors.J. Neurochem. 55 541550.
  • 52
    Sinclair C., Shepel P., Geiger J., Parkinson F. (2000) Stimulation of nucleoside efflux and inhibition of adenosine kinase by A1 adenosine receptor activation.Biochem. Pharmacol. 59 477483.
  • 53
    Spragg R.G., Hinshaw D.B., Hyslop P.A., Schraufstatter I.U., Cochrane C.G. (1985) Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388D1 cells after oxidant injury.J. Clin. Invest. 76 14711476.
  • 54
    Stanness K.A., Westrum L.E., Fornaciari E., Mascagni P., Nelson J.A., Stenglein S.G., Myers T., Janigro D. (1997) Morphological and functional characterization of anin vitro blood-brain barrier model.Brain Res. 771 329342.
  • 55
    Sweeney M.I., White T.D., Sawynok J. (1993) Morphine-evoked release of adenosine from the spinal cord occurs via a nucleoside carrier with differential sensitivity to dipyridamole and nitrobenzylthioinosine [published erratum appears in Brain Res. (1993) 618, 179].Brain Res. 614 301307.
  • 56
    Thampy K.G. & Barnes E.M.J r. (1983) Adenosine transport by cultured glial cells from chick embryo brain.Arch. Biochem. Biophys. 220 340346.
  • 57
    Von Lubitz D.K. (1999) Adenosine and cerebral ischemia: therapeutic future or death of a brave concept?Eur. J. Pharmacol. 365 925.
  • 58
    Ward J.L., Sherali A., Mo Z.P., Tse C.M. (2000) 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 83758381.
  • 59
    Whittingham T.S. (1990) Aspects of brain energy metabolism and cerebral metabolism, inCerebral Ischemia and Resuscitation (Schurr A. and Rigor B. M., eds), pp. 101121. CRC Press, Boca Raton, Florida.
  • 60
    Worku Y. & Newby A.C. (1982) Nucleoside exchange catalysed by the cytoplasmic 5′-nucleotidase. Biochem. J. 205 503510.
  • 61
    Yao S.Y., Ng A.M., Muzyka W.R., Griffiths M., Cass C.E., Baldwin S.A., Young J.D. (1997) Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues.J. Biol. Chem. 272 2842328430.