• H. Zimmermann
Part of the Purinergic and Pyrimidinergic Signalling book series (HEP, volume 151 / 1)


Ecto-nucleotidases are cell surface-located enzymes which catalyze extra-cellular nucleotide hydrolysis. An extracellular hydrolysis pathway for nucleotides has been detected in essentially all tissues and also in a large variety of cell culture systems. Its general features include the following:
  1. 1.

    Nucleoside 5′-triphosphates are sequentially metabolized to the nucleoside with nucleoside 5′-diphosphate and nucleoside 5′-monophosphate appearing as intermediate products. The nucleoside may then be further deaminated to inosine by adenosine deaminase (Franco et al. 1997).

  2. 2.

    Not only ATP, ADP, and AMP but essentially all physiologically occurring purine and pyrimidine nucleotides are hydrolyzed.

  3. 3.

    Extracellular hydrolysis of nucleotides is not inhibited by known inhibitors of intracellular ATPases such as P-type, F-type, and V-type ATPases.

  4. 4.

    Nucleotide hydrolysis depends on divalent cations, generally millimolar concentrations of either Ca2+ or Mg2+.

  5. 5.

    Nucleotide hydrolysis has an alkaline pH optimum.

  6. 6.

    A major function of the extracellular enzyme chain appears to be the termination of the physiological action of nucleotides released from cells.

To date no information is available as to whether the hydrolysis of ATP is used to drive energy-dependent processes (for reviews of the earlier work see Arch and Newsholme 1978; Fox 1978; Pearson 1985; Dhalla and Zhao 1988; Ziganshin et al. 1994a; Plesner 1995; Sarkis et al. 1995; Beaudoin et al. 1996; Zimmermann 1996a,b; Plesner et al. 1997; Zimmermann and Pearson 1998).


Extracellular Nucleotide Diadenosine Polyphosphates Torpedo Electric Organ Neural Cell Adhesion Mole Human NTPDase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Airas L (1998) CD73 and adhesion of B-Cells to follicular dendritic cells. Leuk Lymphoma 29: 37–47PubMedCrossRefGoogle Scholar
  2. Aleo MF, Sestini S, Pompucci G, Preti A (1996) Enzymatic activities affecting exogenous nicotinamide adenine dinucleotide in human skin fibroblasts. J Cell Physiol 167: 173–176PubMedCrossRefGoogle Scholar
  3. Arch JRS, Newsholme EA (1978) The control of the metabolism and the hormonal role of adenosine. In: Campbell PN, Aldridge WN (eds) Essays in biochemistry 14. Academic Press, London, pp 82–123Google Scholar
  4. Asai T, Miura S, Sibley LD, Okabayashi H, Takeuchi T (1995) Biochemical and molecular characterization of nucleoside triphosphate hydrolase isozymes from the parasitic protozoan Toxoplasrna gondii. J Biol Chem 270: 11391–11397PubMedCrossRefGoogle Scholar
  5. Aurivillius M, Hansen OC, Lazrek MBS, Bock E, ()brink B (1990) The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of the immunoglobulin superfamily. FEBS Lett 264: 267–269Google Scholar
  6. Bächner D, Ahrens M, Betat N, Schröder D, Gross G (1999) Developmental expression analysis of murine autotaxin ( ATX ). Mech Develop 84: 121–125Google Scholar
  7. Bailey SJ, Hourani SMO (1995) Effects of suramin on contractions of the guinea-pig vas deferens induced by analogues of adenosine 5’-triphosphate. Br J Pharmacol 114: 1125–1132PubMedCrossRefGoogle Scholar
  8. Barbacci E, Filippini A, Decesaris P, Ziparo E (1996) Identification and characterization of an ecto-ATPase activity in rat Sertoli cells. Biochem Biophys Res Commun 222: 273–279PubMedCrossRefGoogle Scholar
  9. Barcellos CK, Schetinger MRC, Dias RD, Sarkis JJF (1998) In vitro effect of central nervous system active drugs on the ATPase-ADPase activity and acetyl-cholinesterase activity from cerebral cortex of adult rats. Gen Pharmacol 31: 563–567PubMedCrossRefGoogle Scholar
  10. Barret J-M, Ernould A-P, Rouillion M-H, Ferry G, Genton A, Boutin JA (1999) Studies of the potency of protein kinase inhibitors on ATPase activities. Chem Biol Interact 86: 17–27CrossRefGoogle Scholar
  11. Battastini AMO, da Rocha JBT, Barcellos CK, Dias RD, Sarkis JJF (1991) Characterization of an ATP diphosphohydrolase (EC in synaptosomes from cerebral cortex of adult rats. Neurochem Res 16: 1303–1310PubMedCrossRefGoogle Scholar
  12. Battastini AMO, Oliveira EM, Moreira CM, Bonan CD, Sarkis JJF, Dias RD (1995) Solubilization and characterization of an ATP diphosphohydrolase (EC from rat brain synaptic plasma membranes. Biochem Mol Biol Int 37: 209–219PubMedGoogle Scholar
  13. Beaudoin AR, Sévigny J, Grondin G, Daoud S, Levesque FP (1997) Purification, characterization, and localization of two ATP diphosphohydrolase isoforms in bovine heart. Am J Physiol 273: H673 — H681PubMedGoogle Scholar
  14. Beaudoin AR, Sévigny J, Picher M (1996) ATP-diphosphohydrolases, apyrases, and nucleotide phosphohydrolases: Biochemical properties and functions. Biomembranes 5: 369–401Google Scholar
  15. Belli SI, Mercuri FA, Sali A. Goding JW (1995) Autophosphorylation of PC-1 (alkaline phosphodiesteraseI/nucleotide pyrophosphatasse) and analysis of the active site. Eur J Biochem 228: 669–676Google Scholar
  16. Belli SI, Sali A, Goding JW (1994) Divalent cations stabilize the conformation of plasma cell membrane glycoprotein PC-1 (alkaline phosphodiesterase I). Biochem J 304: 75–80PubMedGoogle Scholar
  17. Belli SI, van Driel IR, Goding JW (1993) Identification and characterization of soluble form of the plasma cell membrane glycoprotein PC-1 (5’-nucleotide phosphodiesterase). Eur J Biochem 217: 421–428PubMedCrossRefGoogle Scholar
  18. Betto R, Senter L, Ceoldo S. Tarricone E, Biral D, Salviati G (1999) Ecto-ATPase activity of alpha-sarcoglycan ( Adhalin ). J Biol Chem 274: 7907–7912Google Scholar
  19. Beukers MW, Kerkhof CJM. Van Rhee MA, Ardanuy U, Gurgel C, Widjaja H, Nickel P, Ijzerman AP, Soudijn W (1995) Suramin analogs, divalent cations and ATP gamma S as inhibitors of ecto-ATPase. Naunyn-Schmiedebergs Arch Pharmacol 351: 523–528PubMedGoogle Scholar
  20. Biederbick A, Rose S, Elsässer HP (1999) A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles. J Cell Sci 112: 2473–2484PubMedGoogle Scholar
  21. Bonan CD, Battastini AMO, Schetinger MRC, Moreira CM, Frassetto SS, Dias RD, Sarkis JJF (1997) Effects of 9-amino-1,2,3,4-tetrahydroacridine (THA) on ATP diphosphohydrolase (EC and 5’-nucleotidase (EC from rat brain synaptosomes. Gen Pharmacol 28: 761–766PubMedCrossRefGoogle Scholar
  22. Bonan CD, Dias MM, Battastini AMO, Dias RD, Sarkis JJF (1998) Inhibitory avoidance learning inhibits ectonucleotidase activities in hippocampal synaptosomes of adult rats. Neurochem Res 23: 977–982PubMedCrossRefGoogle Scholar
  23. Braren R, Glowacki G, Nissen M, Haag F, Koch-Nolte F (1998) Molecular characterization and expression of the gene for mouse NAD’: arginine ecto-mono(ADPribosyl)transferase. Biochem J 336: 561–568PubMedGoogle Scholar
  24. Braun N, Lenz C, Gillardon F, Zimmermann M, Zimmermann H (1997) Focal cerebral ischemia enhances glial expression of 5’-nucleotidase. Brain Res 766: 213–226PubMedCrossRefGoogle Scholar
  25. Braun N, Zhu Y, Krieglstein J, Culmsee C, Zimmermann H (1998) Upregulation of the enzyme chain hydrolyzing extracellular ATP following transient forebrain ischemia in the rat. J Neurosci 18: 4891–4900PubMedGoogle Scholar
  26. Brownhill VR, Hourani SMO, Kitchen I (1997) Ontogeny of P2-purinoceptors in the longitudinal muscle and muscularis mucosae of the rat isolated duodenum. Br J Pharmacol 122: 225–232PubMedCrossRefGoogle Scholar
  27. Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW (1990) Plasma membrane glycoprotein PC-1: eDNA cloning of the human molecule, amino acid sequence and chromosomal location. J Biol Chem 265: 17506–17511PubMedGoogle Scholar
  28. Bultmann R, Starke K (1995) Reactive red 2: A P2y-selective purinoceptor antagonist and an inhibitor of ecto-nucleotidase. Naunyn-Schmiedebergs Arch Pharmacol 352: 477–482PubMedGoogle Scholar
  29. Bultmann R, Driessen B, Goncalves J, Starke K (1995) Functional consequences of inhibition of nucleotide breakdown in rat vas deferens: A study with Evans blue. Naunyn-Schmiedebergs Arch Pharmacol 351: 555–560Google Scholar
  30. Bultmann R, Pause B, Wittenburg H, Kurz G, Starke K (1996a) P2-purinoceptor antagonists.1. Blockade of P2-purinoceptor subtypes and ecto-nucleotidases by small aromatic isothiocyanato-sulphonates. Naunyn Schmiedebergs Arch Pharmacol 354: 481–490PubMedCrossRefGoogle Scholar
  31. Bultmann R, Wittenburg H, Pause B, Kurz G, Nickel P, Starke K (1996b) P-purinoceptor antagonists. e3. Blockade of P2-purinoceptor subtypes and ecto-nucleotidases by compounds related to suramin. Naunyn Schmiedebergs Arch Pharmacol 354: 498–504PubMedCrossRefGoogle Scholar
  32. Cardenal A, Masuda I, Ono W, Haas AL, Ryan LM, Trotter D, Mccarty DJ (1998) Serum nucleotide pyrophosphohydrolase activity; elevated levels in osteoarthritis, calcium pyrophosphate crystal deposition disease, scleroderma, and fibromyalgia. J Rheumatol 25: 2175–2180PubMedGoogle Scholar
  33. Carl SAL, Smith TM, Kirley TL (1998) Cross-linking induces homodimer formation and inhibits enzymatic activity of chicken stomach ecto-apyrase. Biochem Mol Biol Int 44: 463–470Google Scholar
  34. Cascalheira JF, Sebastiao AM (1992) Adenine nucleotide analogues, including rphosphate-substituted analogues, are metabolized extracellularly in innervated frog sartorius muscle. Eur J Pharmacol 222: 49–59PubMedCrossRefGoogle Scholar
  35. Chadwick BP, Frischauf AM (1997) Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes. Mamm Genome 8: 668–672PubMedCrossRefGoogle Scholar
  36. Chadwick BP, Frischauf AM (1998) The CD39-like gene family: Identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster. Genomics 50: 357–367PubMedCrossRefGoogle Scholar
  37. Chadwick BP, Williamson J, Sheer D, Frischauf AM (1998) cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases. Mamm Genome 9: 162–164Google Scholar
  38. Chen BC, Lee CM, Lin WW (1996) Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial cells, C-6 glioma cells and RAW 264.7 macrophages. Br J Pharmacol 119: 1628–1634PubMedCrossRefGoogle Scholar
  39. Cheung PK, Visser J, Bakker WW (1994) Upregulation of antithrombotic ectonucleotidases by aspirin in human endothelial cells in-vitro. J Pharm Pharmacol 46: 1032–1034PubMedCrossRefGoogle Scholar
  40. Cheung PK, Klok PA, Bakker WW (1996) Minimal change-like glomerular alterations induced by a human plasma factor. Nephron 74: 586–593PubMedCrossRefGoogle Scholar
  41. Christensen LD (1997) CD73 (ecto-5’-nucleotidase) on blood mononuclear cells. Regulation of ecto-5’-nucleotidase activity and antigenic heterogeneity of CD73 on blood mononuclear cells from healthy donors and from patients with immunodeficiency. APMIS 105:5–28: 5–28Google Scholar
  42. Christoforidis S, Papamarcaki T, Galaris D, Kellner R, Tsolas 0 (1995) Purification and properties of human placental ATP diphosphohydrolase. Eur J Biochem 234: 66–74Google Scholar
  43. Christoforidis S, Papamarcaki T, Tsolas 0 (1996) Human placental ATP diphosphohydrolase is a highly N-glycosylated plasma membrane enzyme. Biochim Biophys Acta (Biomemb) 1282: 257–262Google Scholar
  44. Clair T, Lee HY, Liotta LA, Stracke ML (1997a) Autotaxin is an exoenzyme possessing 5’-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem 272: 996–1001PubMedCrossRefGoogle Scholar
  45. Clair T, Krutzsch HC, Liotta LA, Stracke ML (1997b) Nucleotide binding to autotaxin: Crosslinking of bound substrate followed by lysC digestion identifies two labeled peptides. Biochem Biophys Res Commun 236: 449–454Google Scholar
  46. Cockayne DA, Muchamuel T, Grimaldi JC, Muller-Steffner H, Randall TD, Lund FE, Murray R, Schuber F, Howard MC (1998) Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood 92: 1324–1333PubMedGoogle Scholar
  47. Coleman JE (1992) Structure and mechanism of alkaline phosphatase. Ann Rev Biophys Biomol Struct 21: 441–483CrossRefGoogle Scholar
  48. Coté YP, Quellet S, Beaudoin A (1992) Kinetic properties of type-II ATP diphosphohydrolase from the tunica media of the bovine aorta. Biochim Biophys Acta 1160: 246–250PubMedCrossRefGoogle Scholar
  49. Crack BE, Beukers MW, McKechnie KCW, Ijzerman AP, Leff P (1994) Pharmacological analysis of ecto-ATPase inhibition: evidence for combined enzyme inhibition and receptor antagonism in P2X purinoceptor ligands. Br J Pharmacol 113: 1432–1438PubMedCrossRefGoogle Scholar
  50. Crack BE, Pollard CE, Beukers MW, Roberts SM, Hunt SF, Ingall AH, McKechnie KCW, Ijzerman TP, Leff P (1995) Pharmacological and biochemical analysis of FPL 67156, a novel, selective inhibitor of ecto-ATPase. Br J Pharmacol 114: 475–481PubMedCrossRefGoogle Scholar
  51. Cunha RA, Sebastiao AM, Ribeiro JA (1998) Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A(1) receptors. J Neurosci 18: 1987–1995PubMedGoogle Scholar
  52. da Silva CP, Schweitzer K, Heyer P, Malavasi F, Mayr GW, Guse AH (1998) Ectocellular CD38-catalyzed synthesis and intracellular Cat+- signalling activity of cyclic ADP-ribose in T- lymphocytes are not functionally related. FEBS Lett 439: 291–296PubMedCrossRefGoogle Scholar
  53. Dalmau I. Vela JM, Gonzalez B, Castellano B (1998) Expression of purine metabolism-related enzymes by microglial cells in the developing rat brain. J Comp Neurol 398: 333–346PubMedCrossRefGoogle Scholar
  54. Damer S. Niebel B, Czeche S, Nickel P, Ardanuy U, Schmalzing G, Rettinger J, Mutschler E, Lambrecht G (1998) NF279: a novel potent and selective antagonist of P2X receptor-mediated responses. Eur J Pharmacol 350: R5 - R6PubMedCrossRefGoogle Scholar
  55. De Flora A, Guida L, Franco L, Zocchi E, Pestarino M, Usai C, Marchetti C, Fedele E, Fontana G, Raiteri M (1996) Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum. Biochem J 320: 665–672PubMedGoogle Scholar
  56. De Flora A, Guida L, Franco L, Zocchi E (1997) The CD38/cyclic ADP-ribose system: A topological paradox. Int J Biochem Cell Biol 29: 1149–1166Google Scholar
  57. de Oliveira EM, Battastini AMO, Meirelles MNL, Moreira CM, Dias RD, Sarkis JJF (1997) Characterization and localization of an ATP diphosphohydrolase activity (EC in sarcolemmal membrane from rat heart. Mol Cell Biochem 170: 115–123CrossRefGoogle Scholar
  58. Deaglio S, Morra M, Mallone R, Ausielleo CM, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F (1998) Human CD38 (ADP-ribosyl cyclase) is a counter receptor of CD31, an Ig superfamily member. J Immunol 160: 395402Google Scholar
  59. Deissler H, Lottspeich F, Rajewsky MF (1995) Affinity purification and cDNA cloning of rat neural differentiation and tumor cell surface antigen gp130RB’36 reveals relationship to human and murine PC-1. J Biol Chem 270: 9849–9855PubMedCrossRefGoogle Scholar
  60. Delgado J, Moro G, Saborido A, Megias A (1997) T-tubule membranes from chicken skeletal muscle possess an enzymic cascade for degradation of extracellular ATP. Biochem J 327: 899–907PubMedGoogle Scholar
  61. Deterre P, Gelman L, Gary-Gouy H, Arrieumerlou C, Berthelier V, Tixier EM, Ktorza S, Goding L, Schmitt C, Bismuth G (1996) Coordinated regulation in human T cells of nucleotide-hydrolyzing ecto-enzymatic activities, including CD38 and PC-1. Possible role in the recycling of nicotinamide adenine dinucleotide metabolites. J Immunol 157: 1381–1388Google Scholar
  62. Dhalla NS, Zhao D (1988) Cell membrane Cat-/Mg’ ATPase. Prog Biophys Mol Biol 52: 1–37PubMedCrossRefGoogle Scholar
  63. Dombrowski KE, Ke Y, Thompson LF, Kapp JA (1995) Antigen recognition by CTL is dependent upon ectoATPase activity. J Immunol 154: 6227–6237PubMedGoogle Scholar
  64. Dombrowski KE, Brewer KA, Maleckar JR, Kirley TL, Thomas JW, Kapp JA (1997) Identification and partial characterization of ectoATPase expressed by immortalized B lymphocytes. Arch Biochem Biophys 340: 10–18PubMedCrossRefGoogle Scholar
  65. Dombrowski KE, Ke Y, Brewer KA, Kapp JA (1998) Ecto-ATPase: an activation marker necessary for effector cell function. Immunol Rev 161: 111–118PubMedCrossRefGoogle Scholar
  66. Dunwiddie TV, Diao LH, Proctor WR (1997) Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J Neurosci 17: 7673–7682PubMedGoogle Scholar
  67. Dzhandzhugazyan K, Bock E (1993) Demonstration of (Ca2+-Mg2+)-ATPase activity of the neural cell adhesion molecule. FEBS Lett 336: 279–283PubMedCrossRefGoogle Scholar
  68. Dzhandzhugazyan K, Bock E (1997) Demonstration of an extracellular ATP-binding site in NCAM: Functional implications of nucleotide binding. Biochemistry 36: 15381–15395Google Scholar
  69. Dzhandzhugazyan KN, Kirkin AF, Straten PT, Zeuthen J (1998) Ecto-ATP diphosphohydrolase/CD39 is overexpressed in differentiated human melanomas. FEBS Lett 430: 227–230PubMedCrossRefGoogle Scholar
  70. Ehrlich YH, Kornecki E (1999) Ecto-protein kinases as mediators for the action of secreted ATP in the brain. Prog Brain Res 120: 411–426PubMedCrossRefGoogle Scholar
  71. Enjyoji K, Sévigny J, Lin Y, Frenette P, Christie PD, Schulte am Esch J, Imai M, Edel-berger JM, Rayburn H, Lech M, Beeler DM, Csizmadia E, Wagner DD, Robson SC, Rosenberg RD (1999) Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nature Med 5: 1010–1017PubMedCrossRefGoogle Scholar
  72. Evans WH (1974) Nucleotide pyrophosphatase, a sialoglycoprotein located on the hepatocyte surface. Nature 250: 391–394PubMedCrossRefGoogle Scholar
  73. Faas MM, Bakker WW, Klok PA, Baller JFW, Schuiling GA (1997) Modulation of glomerular ECTO-ADPase expression by oestradiol. A histochemical study. Thromb Haemost 77: 767–771Google Scholar
  74. Fernley HN (1971) Mammalian alkaline phosphatases. In: Boyer PD (ed) The enzymes. Academic Press, New York, pp 417–447Google Scholar
  75. Ferrari D, Chiozzi P, Falzon S, Dal Susino M, Collo G, Buell G, Di Virgilio F (1997) ATP-mediated cytotoxicity in microglial cells. Neuropharmacology 36: 1295–1301PubMedCrossRefGoogle Scholar
  76. Ferrero E, Malavasi F (1997) Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide(+)-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase. J Immunol 159: 3858–3865PubMedGoogle Scholar
  77. Flaherty KM, DeLuca-Flaherty C, Mckay DB (1990) Three-dimensional structure of the ATPase fragment of a 70 K heat-shock cognate protein. Nature 346: 623–628PubMedCrossRefGoogle Scholar
  78. Fox IH (1978) Degradation of purine nucleotides. In: Kelley WN, Weiner IM (eds) Uric acid. Springer, Berlin Heidelberg New York, pp 93–124CrossRefGoogle Scholar
  79. Franco R, Casado V, Ciruela F, Saura C, Mallol J, Canela EI, Lluis C (1997) Cell surface adenosine deaminase: much more than an ectoenzyme. Prog Neurobiol 52: 283–294PubMedCrossRefGoogle Scholar
  80. Frassetto SS, Dias RD, Sarkis JJF (1993) Characterization of an ATP disphosphohydrolase activity (APYRASE, EC in rat blood platelets. Mol Cell Biochem 129: 47–55PubMedCrossRefGoogle Scholar
  81. Funaro A, Horenstein AL, Malavasi F (1995) Human CD38: a versatile leukocyte molecule with emerging clinical prospects. Fund Clin Pharmacol 3: 101–113Google Scholar
  82. Funaro A, Horenstein AL, Calosso L, Morra M, Tarocco RP, Franco L, De Flora A, Malavasi F (1996) Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids. Int Immunol 8: 1643–1650PubMedCrossRefGoogle Scholar
  83. Fuss B, Baba H, Phan T, Tuohy VK, Macklin WB (1997) Phosphodiesterase I, a novel adhesion molecule and/or cytokine involved in oligodendrocyte function. J Neurosci 17: 9095–9103PubMedGoogle Scholar
  84. Gao L, Dong LQ, Whitlock JP (1998) A novel response to dioxin — Induction of ectoATPase gene expression. J Biol Chem 273: 15358–15365PubMedCrossRefGoogle Scholar
  85. Gasmi L, Cartwright JL, McLennan AG (1998) The hydrolytic activity of bovine adrenal medullary plasma membranes towards diadenosine polyphosphates is due to alkaline phosphodiesterase-I. Biochim Biophys Acta 1405: 121–127PubMedCrossRefGoogle Scholar
  86. Gayle RB, Maliszewski CR, Gimpel SD, Schoenborn MA, Caspary RG, Richards C, Brasel K, Price V, Drosopoulos JHF, Islam N, Alyonycheva TN, Broekman MJ, Marcus AJ (1998) Inhibition of platelet function by recombinant soluble ectoADPase/CD39. J Clin Invest 101: 1851–1859PubMedCrossRefGoogle Scholar
  87. Goding JW, Terkeltaub R, Maurice M, Deterre P, Sali A, Belli SI (1998) Ecto-phosphodiesterase/pyrophosphatase of lymphocytes and non-lymphoid cells: structure and function of the PC-1 family. Immunol Rev 161: 11–26PubMedCrossRefGoogle Scholar
  88. Gordon EL, Pearson JD, Dickinson ES, Moreau D, Slakey LL (1989) The hydrolysis of extracellular adenine nucleotides by arterial smooth muscle cells; Regulation of adenosine production at the cell surface. J Biol Chem 264: 18986–18992Google Scholar
  89. Grobben B, Anciaux K, Roymans D, Stefan C, Bollen M, Esmans EL, Siegers H (1999) An ecto-nucleotide pyrophosphatase is one of the main enzymes involved in the extracellular metabolism of ATP in rat C6 glioma. J Neurochem 72: 826–834PubMedCrossRefGoogle Scholar
  90. Haag F, Koch-Nolte F, Gerber A, Schroder J, Thiele HG (1997) Rat T cell differentiation alloantigens RT6.1 and RT6.2 are NADtmetabolizing ecto-enzymes that differ in their enzymatic activities. Transplant Proc 29: 1699–1700PubMedCrossRefGoogle Scholar
  91. Handa M, Guidotti G (1996) Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from potato tubers (Solanum tuberosum). Biochem Biophys Res Commun 218: 916–923PubMedCrossRefGoogle Scholar
  92. Harahap AR, Goding JW (1988) Distribution of the murine plasma cell antigen PC-1 in non-lymphoid cells. J Immunol 141: 2317–2320PubMedGoogle Scholar
  93. Harden TK, Lazarowski ER, Boucher RC (1997) Release, metabolism and interconversion of adenine and uridine nucleotides: Implications for G protein-coupled P2 receptor agonist selectivity. Trends Pharmacol Sci 18: 43–46PubMedCrossRefGoogle Scholar
  94. Heine P, Braun N, Zimmermann H (1999) Functional characterization of rat ectoATPase and ecto-ATP diphosphohydrolase after heterlogous expression in CHO cells. Eur J Biochem 262: 102–107PubMedCrossRefGoogle Scholar
  95. Hirata O, Kimura N, Sato K, Ohsugi Y, Takasawa S, Okamoto H, Ishikawa J, Kaisho T, Ishihara K, Hirano T (1994) ADP ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule, BST-1. FEBS Lett 356: 244–248PubMedCrossRefGoogle Scholar
  96. Hollmann C, Haag F, Schlott M, Damaske A, Bertuleit H, Matthes M, Kuhl M, Thiele HG, Koch-Nolte F (1996) Molecular characterization of mouse T-cell ecto-ADPribosyltransferase Rt6: Cloning of a second functional gene and identification of the Rt6 gene products. Mol Immunol 33: 807–817PubMedCrossRefGoogle Scholar
  97. Hosoda N, Hoshino S, Kanda Y, Katada T (1999) Inhibition of phosphodiesterase/ pyrophosphatase activity of PC-1 by its association with glycosaminoglycans. Eur J Biochem 265: 763–770PubMedCrossRefGoogle Scholar
  98. Hourani SMO, Chown JA (1989) The effects of some possible inhibitors of ectonucleotidases on the breakdown and pharmacological effects of ATP in the guinea-pig urinary bladder. Gen Pharmacol 4: 413–416Google Scholar
  99. Hourani SMO, Bailey SJ, Nicholls J, Kitchen I (1991) Direct effects of adenylyl 5’-(ß,y-methylene)diphosphonate, a stable ATP analogue, on relaxant P1-purinoceptors in smooth muscle. Br J Pharmacol 104: 685–690PubMedCrossRefGoogle Scholar
  100. Imai M, Kaczmarek E, Koziak K, Sévigny J, Goepfert C, Guckelberger O, Csizmadia E, Esch JSA, Robson SC (1999) Suppression of ATP diphosphohydrolase/CD39 in human vascular endothelial cells. Biochemistry 38: 13473–13479PubMedCrossRefGoogle Scholar
  101. Itami C, Taguchi R, Ikezawa H, Nakabayashi T (1997) Release of ectoenzymes from small intestine brush border membranes of mice by phospholipases. Biosci Biotechnol Biochem 61: 336–340PubMedCrossRefGoogle Scholar
  102. James S, Richardson PJ (1993) Production of adenosine from extracellular ATP at the striatal cholinergic synapse. J Neurochem 60: 219–227PubMedCrossRefGoogle Scholar
  103. James SG, Appleby GJ, Miller KA, Steen JT, Colquhoun EQ, Clark MG (1996) Purine and pyrimidine nucleotide metabolism of vascular smooth muscle cells in culture. Gen Pharmacol 27: 837–844PubMedCrossRefGoogle Scholar
  104. Jin-Hua P, Goding JW, Nakamura H, Sano K (1997) Molecular cloning and chromosomal localization of PD-I? (PDNP3), a new member of the human phosphodiesterase I genes. Genomics 45: 412–415PubMedCrossRefGoogle Scholar
  105. Johnson CR, Charlton SJ, Hourani SMO (1996) Responses of the longitudinal muscle and the muscularis mucosac of the rat duodenum to adenine and uracil nucleotides. Br J Pharmacol 117: 823–830PubMedCrossRefGoogle Scholar
  106. Kaczmarek E, Koziak K, Sévigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC (1996) Identification and characterization of CD39 vascular ATP diphosphohydrolase. J Biol Chem 271: 33116–33122PubMedCrossRefGoogle Scholar
  107. Kaczmarek E, Siegel JB, Sévigny J, Koziak K, Hancock WW, Beaudoin A, Bach FH, Robson SC (1997) Vascular ATP diphosphohydrolase (CD39/ATPDase). In: Plesner L, Kirley TL, Knowles AF (eds) Ecto-ATPases: recent progress on structure and function. Plenum Press, New York, pp 171–185CrossRefGoogle Scholar
  108. Kaisho T, Ishikawa J, Oritani K, Inazawa J, Tomizawa H, Muraoka O, Ochi T, Hirano T (1994) BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth. Proc Natl Acad Sci USA 91: 5325–5329PubMedCrossRefGoogle Scholar
  109. Kansas GS, Wood GS, Tedder TF (1991) Expression, distribution, and biochemistry of human CD39: Role in activation-associated homotypic adhesion of lymphocytes. J Immunol 146: 2235–2244Google Scholar
  110. Kaplan MM (1986) Serum alkaline phosphatase—another piece is added to the puzzle. Hepatol 6: 526–528CrossRefGoogle Scholar
  111. Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K (1995) Molecular cloning and chromosomal assignment of the humans brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). Genomics 30: 380–384PubMedCrossRefGoogle Scholar
  112. Kawagoe H, Stracke ML, Nakamura H, Sano K (1997) Expression and transcriptional regulation of the PD-I alpha/autotaxin gene in neuroblastoma. Cancer Res. 57: 2516–2521PubMedGoogle Scholar
  113. Kegel B, Braun N, Heine P, Maliszewski CR, Zimmermann H (1997) An ecto-ATPase and an ecto-ATP diphosphohydrolase are expressed in rat brain. Neuropharmacology 36: 1189–1200PubMedCrossRefGoogle Scholar
  114. Kennedy C, Leff P (1995) How should P2X purinoceptors be classified pharmacologically? Trends Pharmacol Sci 16: 168–174PubMedCrossRefGoogle Scholar
  115. Kennedy C, Westfall TD, Sneddon P (1996) Modulation of purinergic neurotransmission by ecto-ATPase. Semin Neurosci 8: 195–199CrossRefGoogle Scholar
  116. Kennedy C, Todorov LD, Mihaylova-Todorova S, Sneddon P (1997) Release of soluble nucleotidases: A novel mechanism for neurotransmitter inactivation? Trends Pharmacol Sci 18: 263–266PubMedGoogle Scholar
  117. Kirley TL (1997) Complementary DNA cloning and sequencing of the chicken muscle Ecto-ATPase — Homology with the lymphoid cell activation antigen CD39. J Biol Chem 272: 1076–1081PubMedCrossRefGoogle Scholar
  118. Kittel A (1997) Role of ecto-ATPases, based on histochemical investigations: Evidences and doubts. In: Plesner L, Kirley TL, Knowles AF (eds) EctoATPases: Recent progress on structure and function. Plenum Press, New York, pp 65–72Google Scholar
  119. Kittel A, Siklôs L, Thurôczy G, Somosy Z (1996) Qualitative enzyme histochemistry and microanalysis reveals changes in ultrastructural distribution of calcium and calcium-activated ATPases after microwave irradiation of the medial habenula. Acta Neuropath 92: 362–368PubMedCrossRefGoogle Scholar
  120. Kittel A, Kaczmarek E, Sevigny J, Lengyel K, Csizmadia E, Robson SC (1999) CD39 as a caveolar-associated ectonucleotidase. Biochem Biophys Res Commun 262: 596–599PubMedCrossRefGoogle Scholar
  121. Knowles AE, Nagy AK (1999) Inhibition of an ecto-ATP-diphosphohydrolase by azide. Eur J Biochem 262: 349–357PubMedCrossRefGoogle Scholar
  122. Knöfel T, Sträter N (1999) X-ray structure of the Escherichia coil periplasmic 5’nucleotidase containing a dimetal catalytic site. Nat Struct Biol 6: 448–453PubMedCrossRefGoogle Scholar
  123. Kohring K, Zimmermann H (1998) Upregulation of ecto-5’-nucleotidase in human neuroblastoma SH-SY5Y cells on differentiation by retinoic acid or phorbolester. Neurosci Lett 258: 127–130PubMedCrossRefGoogle Scholar
  124. Koyamada N, Miyatake T, Candinas D, Hechenleitner P, Siegel J, Hancock WW, Bach FH, Robson SC (1996) Apyrase administration prolongs discordant xenograft survival. Transplantation 62: 1739–1743PubMedCrossRefGoogle Scholar
  125. Kumakura S, Maddux BA, Sung CK (1998) Overexpression of membrane glycoprotein PC-1 can influence insulin action at a post-receptor site. J Cell Biochem 68: 366–377PubMedCrossRefGoogle Scholar
  126. Kübler D, Pyerin W, Kinzel V (1980) Generation of pyrophosphate from extracellular ATP at the surface of HeLa cells. Eur J Cell Biol 21: 231–233PubMedGoogle Scholar
  127. Landt M, Butler LG (1978) 5’-nucleotide phosphodiesterase: Isolation of covalently bound 5’-adenosine monophosphate, an intermediate in the catalytic cycle. Biochemistry 17: 4130–4135Google Scholar
  128. Lazarowski ER, Homolya L, Boucher RC, Harden TK (1997) Identification of an ectonucleoside diphosphokinase and its contribution to interconversion of P2 receptor agonists. J Biol Chem 272: 20402–20407PubMedCrossRefGoogle Scholar
  129. LeBel D, Poirier GG, Phaneuf S, St.-Jean P, Laliberté JF, Beaudoin AR (1980) Characterization and purification of a calcium-sensitive ATP diphosphohydrolase from pig pancreas. J Biol Chem 255: 1227–1233PubMedGoogle Scholar
  130. Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA, Stracke ML (1996a) Cloning chromosomal localization, and tissue expression of autotaxin from human tetracarcinoma cells. Biochem Biophys Res Commun 218: 714–719PubMedCrossRefGoogle Scholar
  131. Lee HY, Clair T, Mulvaney PT, Woodhouse EC, Aznavoorian S, Liotta LA, Stracke ML (1996b) Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin. J Biol Chem 271: 24408–24412PubMedCrossRefGoogle Scholar
  132. Lewis Carl S, Kirley TL (1997) Immunolocalization of the ecto-ATPase and ectoapyrase in chicken gizzard and stomach — Purification and N-terminal sequence of the stomach ecto-apyrase. J Biol Chem 272: 23645–23652CrossRefGoogle Scholar
  133. Lin S-H, Guidotti G (1989) Cloning and expression of a cDNA coding for a rat liver plasma membrane ecto-ATPase. The primary structure of the ecto-ATPase is similar to that of the human biliary glycoprotein I. J Biol Chem 264: 14408–14414Google Scholar
  134. Lund F, Solvason N, Grimaldi JC, Parkhouse RME, Howard M (1995) Murine CD38: An immunoregulatory ectoenzyme. Immunol Today 16: 469–473Google Scholar
  135. Lund FE, Cockayne DA, Randall TD, Solvason N, Schuber F, Howard MC (1998) CD38: A new paradigm in lymphocyte activation and signal transduction. Immunol Rev 161:79–93: 79–93Google Scholar
  136. Lüthje J, Ogilvie A (1987) Catabolism of AP4A and Ap3A in human serum. Identification of isoenzymes and their partial characterization. Eur J Biochem 169: 385–388Google Scholar
  137. Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Soencer S, Grupe A, Henzel W, Stewart TA (1995) Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 373: 448–451PubMedCrossRefGoogle Scholar
  138. Maliszewski CR, DeLepesse GJT, Schoenborn MA, Armitage RJ, Fanslow WC, Nakajima T, Baker E, Sutherland GR, Poindexter K, Birks C, Alpert A, Friend D, Gimpel SD, Gayle RB (1994) The CD39 lymphoid cell activation antigen: Molecular cloning and structural characterization. J Immunol 153: 3574–3583Google Scholar
  139. Mallone R, Ferrua S, Morra M, Zocchi E, Mehta K, Notarangelo LD, Malavasi F (1998) Characterization of a CD38-like 78-kilodalton soluble protein released from B cell lines derived from patients with X-linked agammaglobulinemia. J Clin Invest 101: 2821–2830PubMedCrossRefGoogle Scholar
  140. Marcus AJ, Broekman MJ, Drosopoulos JHF, Islam N, Alyonycheva TN, Safier LB, Hajjar KA, Posnett DN, Schoenborn MA, Schooley KA, Gayle RB, Maliszewski CR (1997) The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39. J Clin Invest 99: 1351–1360PubMedCrossRefGoogle Scholar
  141. Marti E, Canti C, Gomez de Aranda I, Miralles F, Solsona C (1996a) Action of suramin upon ecto-apyrase activity and synaptic depression of Torpedo electric organ. Br J Pharmacol 118: 1232–1236PubMedCrossRefGoogle Scholar
  142. Marti E, Gomez de Aranda I, Solsona C (1996b) Inhibition of ATP-diphosphohydrolase (apyrase) of Torpedo electric organ by 5’-p-fluorosulfonvlbenzoyladenosine. Biochim Biophys Acta (Biomembranes) 1282: 17–24CrossRefGoogle Scholar
  143. Mateo J, Rotllan P, Miras-Portugal MT (1996) Suramin — a powerful inhibitor of neural ecto-adenosine polyphosphate hydrolase. Br J Pharmacol 119: 1–2PubMedCrossRefGoogle Scholar
  144. Mateo J, Rotllan P, Marti E, Gomez de Aranda I, Salsona C, Miras-Portugal MT (1997a) Diadenosine polyphosphate hydrolase from presynaptic plasma membranes of Torpedo electric organ. Biochem J 323: 677–684PubMedGoogle Scholar
  145. Mateo J, Miras-Portugal MT, Rotllan P (1997b) Ecto-enzymatic hydrolysis of diadenosine polyphosphates by cultured adenomedullary vascular endothelial cells. Am J Physiol Cell Physiol 42: C918–C927Google Scholar
  146. Mateo J, Harden TK, Boyer JL (1999) Functional expression of a cDNA encoding a human ecto-ATPase. Br J Pharmacol 128: 396–402PubMedCrossRefGoogle Scholar
  147. Meerson NR, Delautier D, Durand-Schneider A-M, Moreau A, Schilsky ML, Sternlieb I, Feldmann G, Maurice M (1998) Identification of B10, an alkaline phosphodiesterase of the apical plasma membrane of hepatocytes and biliary cells, in rat serum: Increased levels following bile duct ligation and during the development of cholagiocarcinoma. Hepatol 27: 563–568Google Scholar
  148. Meghji P, Burnstock G (1995) Inhibition of extracellular ATP degradation in endothelial cells. Life Sci 57: 763–771PubMedCrossRefGoogle Scholar
  149. Meghji P, Pearson JD, Slakey LL (1995) Kinetics of extracellular ATP hydrolysis by microvascular endothelial cells from rat heart. Biochem J 308: 725–731PubMedGoogle Scholar
  150. Mehta K, Shahid U, Malavasi F (1996) Human CD38, a cell-surface protein with multiple functions. FASEB J 10: 1408–1417PubMedGoogle Scholar
  151. Miledi R, Molenaar PC, Polak RL (1984) Acetylcholinesterase activity in intact and homogenized skeletal muscle of the frog. J Physiol London 349: 663–686PubMedGoogle Scholar
  152. Minelli A, Moroni M, Trinari D, Mezzasoma I (1997) Hydrolysis of extracellular adenine nucleotides by equine epidydimal spermatozoa. Comp Biochem Physiol [B] 117: 531–534CrossRefGoogle Scholar
  153. Morley DJ, Hawley DM, Ulbright DM, Butler LG, Culp JS, Hodes ME (1987) Distribution of phosphodiesterase I in normal human tissues. J Histochem Cytochem 35: 75–82PubMedCrossRefGoogle Scholar
  154. Mulero JJ, Yeung G, Nelken ST, Ford JE (1999) CD39–L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates. J Biol Chem 29: 2006420067Google Scholar
  155. Murata J, Lee HJ, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML (1994) cDNA cloning of the human motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem 269: 30479–30484Google Scholar
  156. Nagy AK, Shuster TA, Delgado-Escueta AV (1986) Ecto-ATPase of mammalian synaptosomes: Identification and enzymic characterization. J Neurochem 47: 976–986Google Scholar
  157. Nagy AK, Shuster TA, Delgado-Escueta V (1989) Rat brain synaptosomal ATP:AMPphosphotransferase activity. J Neurochem 53: 1166–1172PubMedCrossRefGoogle Scholar
  158. Nagy AK, Houser CR, Delgado-Escueta AV (1990) Synaptosomal ATPase activities in temporal cortex and hippocampal formation of humans with focal epilepsy. Brain Res 529: 192–201PubMedCrossRefGoogle Scholar
  159. Nagy AK (1997) Ecto-ATPases of the nervous system. In: Plesner L, Kirley TL, Knowles AF (eds) Ecto-ATPases: recent progress in structure and function. Plenum Press, New York, pp 1–13CrossRefGoogle Scholar
  160. Nagy AK, Walton NY, Treiman DM (1997) Reduced cortical ecto-ATPase activity in rat brains during prolonged status epilepticus induced by sequential administration of lithium and pilocarpine. Mol Chem Neuropathol 31: 135–147PubMedCrossRefGoogle Scholar
  161. Nagy AK, Knowles AF, Nagami GT (1998) Molecular cloning of the chicken oviduct ecto-ATP-diphosphohydrolase. J Biol Chem 273: 16043–16049PubMedCrossRefGoogle Scholar
  162. Nakabayashi T, Matsuoka Y, Taguchi R, Ikezawa H, Kimura Y (1993) Proof of alkaline phosphodiesterase-I as a phosphatidylinositol-anchor enzyme. Int J Biochem 25: 689–696PubMedCrossRefGoogle Scholar
  163. Nakabayashi T, Matsuoka Y, Ikezawa H, Kimura Y (1994) Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phosphatidylinositol-specific phosphoIipase C. 4. The release from Cacia porcellus organs. Int J Biochem 26: 171–179PubMedCrossRefGoogle Scholar
  164. Narita M, Goji J, Nakamura H, Sano K (1994) Molecular cloning, expression, and localization of a brain-specific phosphodiesterase I/nucleotide pyrophosphatase ( PD-I alpha) from rat brain. J Biol Chem 269: 28235–28242Google Scholar
  165. Nishina FI, Inageda K, Takahashi K, Hoshino S, Ikeda K, Katada T (1994) Cell surface antigen CD38 identified as ecto-enzyme of NAD glycohydrolase has hyaluronatebinding activity. Biochem Biophys Res Commun 203: 1318–1323PubMedCrossRefGoogle Scholar
  166. Oda Y, Kuo MD, Huang SS, Huang JS (1991) The plasma cell membrane glycoprotein, PC-1, is a threonine-specific protein kinase stimulated by acidic fibroblast growth factor. J Biol Chem 266: 16791–16795PubMedGoogle Scholar
  167. Oda Y, Kuo MD, Huang SS, Huang JS (1993) The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein from bovine liver plasma membranes has aFGF-stimulated kinase, autoadenylation, and alkaline phosphodiesterase activities. J Biol Chem 268: 27318–27326PubMedGoogle Scholar
  168. Ogilvie A, Lüthje J, Pohl U, Busse R (1989) Identification and partial characterization of an adenosine(5’)tetraphospho(5’)adenosine hydrolase on intact bovine aortic endothelial cells. Biochem J 259: 97–103PubMedGoogle Scholar
  169. Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S (1998) Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nature Genet 19: 271–273PubMedCrossRefGoogle Scholar
  170. Oyajobi BO, Russell RGG, Caswell AM (1994) Modulation of ecto-nucleoside triphosphate pyrophosphatase activity of human osteoblast-like bone cells by la,25-dihydroxyvitamin D3, 24R,25-dihydroxyvitamin D3, parathyroid hormone, and dexamethasone. J Bone Miner Res 9: 1259–1266PubMedCrossRefGoogle Scholar
  171. Pain T, Headrick JP (1996) Effects and metabolites of NAD in the perfused rat heart. Drug Develop Res 37: 150Google Scholar
  172. Pappas GD, Kriho V (1988) Fine structural localization of Ca’+-ATPase activity at the forg neuromuscular junction. J Neurocytol 17: 417–423PubMedCrossRefGoogle Scholar
  173. Pearson JD (1985) Ectonucleotidases. Measurememt of activities and use of inhibitors. In: Paton DM (ed) Methods in pharmacology 6. Plenum Press, New York, pp 83–107Google Scholar
  174. Peola S, Borrione P, Matera L, Malavasi F, Pileri A, Massaia M (1996) Selective induction of CD73 expression in human lymphocytes by CD38 ligation: a novel pathway linking signal transducers with ecto-enzyme activities. J Immunol 157: 4354–4362PubMedGoogle Scholar
  175. Peoples RW, Li CY (1998) Inhibition of NMDA-gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones. Br J Pharmacol 124: 400–408PubMedCrossRefGoogle Scholar
  176. Picher M, Coté YP, Béliveau R, Potier M, Beaudoin AR (1993) Demonstration of a novel type of ATP-diphosphohydrolase (EC in the bovine lung. J Biol Chem 268: 4699–4703PubMedGoogle Scholar
  177. Picher M, Beliveau R, Potier M, Savaria D, Rousseau E, Beaudoin AR (1994) Demonstration of an ecto-ATP-diphosphohydrolase (EC in non-vascular smooth muscles of the bovine trachea. Biochim Biophys Acta (Gen Subj) 1200: 167–174CrossRefGoogle Scholar
  178. Picher M, Sévigny J, D’Orléans-Juste P, Beaudoin AR (1996) Hydrolysis of P2purinoceptor agonists by a purified ectonucleotidase from the bovine aorta, the ATP- diphosphohydrolase. Biochem Pharmacol 51: 1453–1460PubMedCrossRefGoogle Scholar
  179. Pilla C, Emanuelli T, Frassetto SS, Battastini AMO, Dias RD, Sarkis JJF (1996) ATP diphosphohydrolase activity (apyrase, EC in human blood platelets. Platelets 7: 225–230PubMedCrossRefGoogle Scholar
  180. Pintor J, Hoyle CHV, Gualix J, Miras-Portugal MT (1997) Mini-Review: Diadenosine polyphosphates in the central nervous system. Neurosci Res Commun 20: 69–78Google Scholar
  181. Plesner L (1995) Ecto-ATPases: identities and functions. Int Rev Cytol 158: 141–214PubMedCrossRefGoogle Scholar
  182. Plesner L, Kirley TL, Knowles AF (eds) (1997) Ecto-ATPases: Recent progress on structure and function. Plenum Press, New YorkGoogle Scholar
  183. Prasad GS, McRee DE, Stura EA, Levitt DG, Lee HC, Stout CD (1996) Crystal structure of aplysia ADP ribosyl cyclase, a homologue of the bifunctional ectozyme CD38. Nat Struct Biol 3: 957–964PubMedCrossRefGoogle Scholar
  184. Ramos A, Pintor J, Miras-Portugal MT, Rotllan P (1995) Use of fluorogenic substrates for detection and investigation of ectoenzymatic hydrolysis of diadenosine polyphosphates: a fluorometric study on chromaffin cells. Anal Biochem 228: 7482CrossRefGoogle Scholar
  185. Rebbe NF, Tong BD, Finley EM, Hickman S (1991) Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1. Proc Natl Acad Sci USA 88: 5192–5196PubMedCrossRefGoogle Scholar
  186. Rebbe NF, Tong BD, Hickman S (1993) Expression of nucleotide pyrophosphatase and alkaline phosphodiesterase I activities of PC-1, the murine plasma cell antigen. Mol Immunol 30: 87–93PubMedCrossRefGoogle Scholar
  187. Redegeld FA, Caldwell CC, Sitkovsky MV (1999) Ecto-protein kinases: ectodomain phosphorylation as a novel target for pharmacological manipulation? Trends Pharmacol Sci 20: 453–459PubMedCrossRefGoogle Scholar
  188. Resta R, Thompson LF (1997) T cell signalling through CD73. Cell Signal 9:131–139 Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109: 95–109Google Scholar
  189. Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH (1997) Loss of ATP diphosphohydrolase activity with endothelial cell activation. J Exp Med 185: 153–163PubMedCrossRefGoogle Scholar
  190. Rodriguez-Pascual F, Torres M, Rotllan P, Miras-Portugal MT (1992) Extracellular hydrolysis of diadenosine polyphosphates, ANA, by bovine chromaffin cells in culture. Arch Biochem Biophys 297: 176–183Google Scholar
  191. Santos AN, Riemann D, Kehlen A, Thiele K, Langner J (1996) Treatment of fibroblast-like synoviocytes with IFN-g results in the downregulation of autotaxin mRNA. Biochem Biophys Res Commun 229: 419–424PubMedCrossRefGoogle Scholar
  192. Sarkis JJF, Battastini AMO, Oliveira EM, Frassetto SS, Dias RD (1995) ATP diphosphohydrolases: an overview. Ciencia e Cultura 47: 131–136Google Scholar
  193. Sarkis JJF, Salto C (1991) Characterization of a synaptosomal ATP diphosphohydrolase from the electric organ of Torpedo marmorata. Brain Res Bull 26: 871–876PubMedCrossRefGoogle Scholar
  194. Sawa H, Kamada K, Sato H, Sendo S, Kondo A, Saito I, Edlund M, ()brink B (1994) C-CAM expression in the developing rat central nervous system. Brain Res Dev Brain Res 78: 35–43CrossRefGoogle Scholar
  195. Schetinger MRC, Falquembach F, Michelot F, Mezzomo A, Rocha JBT (1998a) Heparin modulates adenine nucleotide hydrolysis by synaptosomes from cerebral cortex. Neurochem Int 33: 243–249PubMedCrossRefGoogle Scholar
  196. Schetinger MRC, Bonan CD, Schierholt R, Webber A, Arteni N, Emanuelli T, Dias RD, Sarkis JJF, Netto CA (1998b) Nucleotide hydrolysis in rats submitted to global cerebral ischemia: A possible link between preconditioning and adenosine production. J Stroke Cerebrovasc Dis 7: 281–286Google Scholar
  197. Schoenborn MA, Jenkins NA, Copeland NG, Gilbert DJ, Gayle RB, Maliszewski CR (1998) Gene structure and chromosome location of mouse Cd39 coding for an ecto-apyrase. Cytogenet Cell Genet 81: 287–289PubMedCrossRefGoogle Scholar
  198. Schulte am Esch JSA, Sévigny J, Kaczmarek E, Siegel JB, Imai M, Koziak K, Beaudoin AR, Robson SC (1999) Structural elements and limited proteolysis of CD39 influence ATP diphosphohydrolase activity. Biochemistry 38: 2248–2258CrossRefGoogle Scholar
  199. Schwab DA, Wilson JE (1989) Complete amino acid sequence or rat brain hexokinase, deduced from the cloned cDNA, and a proposed structure of a mammalian hexokinase. Proc Natl Acad Sci USA 86: 2563–2567PubMedCrossRefGoogle Scholar
  200. Scott LJ, Delautier D, Meerson NR, Trugnan G, Goding JW, Maurice M (1997) Biochemical and molecular identification of distinct forms of alkaline phosphodiesterase I expressed on the apical and basolateral plasma membrane surfaces of rat hepatocytes. Hepatol 25: 995–1002CrossRefGoogle Scholar
  201. Servos J, Reiländer H, Zimmermann H (1998) Catalytically active soluble ecto-5’nucleotidase purified after heterologous expression as a tool for drug screening. Drug Develop Res 45: 269–276CrossRefGoogle Scholar
  202. Sévigny J, Picher M, Grondin G, Beaudoin AR (1997a) Purification and immunohistochemical localization of the ATP diphosphohydrolase in bovine lungs. Am J Physiol 272: L939 — L950PubMedGoogle Scholar
  203. Sévigny J, Levesque FP, Grondin G, Beaudoin AR (1997b) Purification of the blood vessel ATP diphosphohydrolase, identification and localisation by immunological techniques. Biochim Biophys Acta (Gen Subj) 1334: 73–88CrossRefGoogle Scholar
  204. Silvennoinen O, Nishigaki H, Kitanaka A, Kumagai M-A, Ito C, Malavasi F, Lin Q, Conley ME, Campana D (1996) CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase Cy and phosphytidylinotisdol 3 kinase. J Immunol 156: 100–107PubMedGoogle Scholar
  205. Slakey LL, Dickinson ES, Goldman SJ, Gordon EL, Meghji P, Pearson JD (1997) The hydrolysis of extracellular adenine nucleotides by cultured vascular cells and cardiac myocytes. In: Plesner L, Kirley TL, Knowles AF (eds) Ecto-ATPases: recent progress on structure and function. Plenum Press, New York, pp 27–32CrossRefGoogle Scholar
  206. Smith TM, Kirley TL, Hennessey TM (1997) A soluble ecto-ATPase from Tetrahymena thermophila: Purification and similarity to the membrane-bound ecto-ATPase of smooth muscle. Arch Biochem Biophys 337: 351–359Google Scholar
  207. Smith TM, Kirley TL (1998) Cloning, sequencing, and expression of a human brain ecto-apyrase related to both the ecto-ATPases and CD39 ecto-apyrases. Biochim Biophys Acta 1386: 65–78PubMedCrossRefGoogle Scholar
  208. Smith T, Carl SAL, Kirley TL (1998) Immunological detection of ecto-ATPase in chicken and rat tissues: Characterization, distribution, and a cautionary note. Biochem Mol Biol Int 45: 1057–1066Google Scholar
  209. Smith TM, Kirley TL (1999a) Glycosylation is essential for functional expression of a human brain ecto-apyrase. Biochemistry 38: 1509–1516PubMedCrossRefGoogle Scholar
  210. Smith TM, Kirley TL (1999b) Site-directed mutagenesis of a human brain ecto-apyrase: evidence that the E-type ATPases are related to the actin/heat shock 70/sugar kinase superfamily. Biochemistry 38: 321–328PubMedCrossRefGoogle Scholar
  211. Smith TM, Carl SAL, Kirley TL (1999) Mutagenesis of two conserved tryptophan residues of the E- type ATPases: inactivation and conversion of an ecto-apyrase to an ecto-NTPase. Biochemistry 38: 5849–5857PubMedCrossRefGoogle Scholar
  212. Snell CR, Snell PH, Richards CD (1984) Degradation of NAD by synaptosomes and its inhibition by nicotinamide mononucleotide: implications for the role of NAD as a synaptic modulator. J Neurochem 43: 1610–1615PubMedCrossRefGoogle Scholar
  213. Solan JL, Deftos LJ, Goding JW, Terkeltaub RA (1996) Expression of the nucleoside triphosphate pyrophosphohydrolase PC-1 is induced by basic fibroblast growth factor ( BFGF) and modulated by activation of the protein kinase A and C pathways in osteoblast-like osteosarcoma cells. J Bone Miner Res 11: 183–192Google Scholar
  214. Sperlagh B, Kittel A, Lajtha A, Vizi ES (1995) ATP acts as fast neurotransmitter in rat habenula: neurochemical and enzymecytochemical evidence. Neuroscience 66: 915–920PubMedCrossRefGoogle Scholar
  215. Stearne PA, van Driel IR, Grego B, Simpson RJ, Goding JW (1985) The murine plasma cell antigen PC-1: purification and partial amino acid sequence. J Immunol 134: 443–448PubMedGoogle Scholar
  216. Stefan C, Stalmans W, Bollen M (1996) Threonine autophosphorylation and nucleotidylation of the hepatic membrane protein PC-1. Eur J Biochcm 241: 338–342CrossRefGoogle Scholar
  217. Stefan C, Stalmans W, Bollen M (1998) Growth-related expression of the ectonucleotide pyrophosphatase PC-1 in rat liver. Hepatol 28: 1497–1503CrossRefGoogle Scholar
  218. Stefan C, Gijsbers R, Stalmans W, Bollen M (1999) Differential regulation of the expression of nucleotide pyrophosphatases phosphodiesterases in rat liver. Biochim Biophys Acta 1450: 45–52PubMedCrossRefGoogle Scholar
  219. Stefanovic V, Ledig M, Mandel P (1976) Divalent cation-activated ecto-nucleoside triphosphatase activity of nervous system cells in tissue culture. J Neurochem 27: 799–805PubMedCrossRefGoogle Scholar
  220. Stefanovic V, Vlahovic P, Ardaillou R (1995) Characterization and control of expression of cell surface alkaline phosphodiesterase I activity in rat mesangial glomerular cells. Renal Physiol Biochem 18: 12–20PubMedGoogle Scholar
  221. Stout JG, Kirley TL (1995) Inhibition of purified chicken gizzard smooth muscle ecto- ATPase by P2 purinoceptor antagonists. Biochem Mol Biol Int 36: 927–934PubMedGoogle Scholar
  222. Stout JG, Kirley TL (1996) Control of cell membrane ecto-ATPase by oligomerization state: intermolecular cross-linking modulates ATPase activity. Biochemistry 35: 8289–8298PubMedCrossRefGoogle Scholar
  223. Stracke ML, Krutzsch HC, Unsworth EJ, Arestad AA, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 267: 2524–2529PubMedGoogle Scholar
  224. Stracke ML, Arestad A, Levine M, Krutzsch HC, Liotta LA (1995) Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility. Melanoma Res 5: 203–209PubMedCrossRefGoogle Scholar
  225. Strobel RS, Nagy AK, Knowles AF, Buegel J, Rosenberg MD (1996) Chicken oviductal ecto-ATP-diphosphohydrolase. Purification and characterization. J Biol Chem 271: 16323–16331Google Scholar
  226. Sud’ina F, Mirzoeva OK, Galkina SI, Pushkareva MA, Ullrich V (1998) Involvement of ecto-ATPase and extracellular ATP in polymorphonuclear granulocyte-endothelial interactions. FEBS Lett 423: 243–248PubMedCrossRefGoogle Scholar
  227. Terrian DM, Hernandez PG, Rea MA, Peters RI (1989) ATP release, adenosine formation, and modulation of dynorphin and glutamic acid release by adenosine analogues in rat hippocampal mossy fiber synaptosomes. J Neurochem 53: 1390–1399PubMedCrossRefGoogle Scholar
  228. Thirion S, Troadec JD, Nicaise G (1996) Cytochemical localization of ecto-ATPses in rat neurohypophysis. J Histochem Cytochem 44: 103–111PubMedCrossRefGoogle Scholar
  229. Todorov LD, Mihaylova Todorova S, Westfall TD, Sneddon P, Kennedy C, Bjur RA, Westfall DP (1997) Neuronal release of soluble nucleotidases and their role in neurotransmitter inactivation. Nature 387: 76–79PubMedCrossRefGoogle Scholar
  230. Torres M, Pintor J, Miras-Portugal MT (1990) Presence of ectonucleotidases in cultured chromaffin cells: hydrolysis of extracellular adenine nucleotides. Arch Biochem Biophys 279: 37–44PubMedCrossRefGoogle Scholar
  231. Tuluc F, Bultmann R, Glanzel M, Frahm AW, Starke K (1998) P2-receptor antagonists. 4. Blockade of P2-receptor subtypes and ecto-nucleotidases by compounds related to reactive blue 2. Naunyn Schmiedebergs Arch Pharmacol 357: 111–120PubMedCrossRefGoogle Scholar
  232. van Driel IR, Goding JW (1987) Plasma cell membrane glycoprotein PC-1: primary structure deduced from cDNA clones. J Biol Chem 262: 4882–4887PubMedGoogle Scholar
  233. van Son WJ, Wit F, van Balen OLB, Tegzess AM, Ploeg RJ, Bakker WW (1997) Decreased expression of glomerular ecto-ATPase in kidney grafts with delayed graft function. Transplant Proc 29: 352–354PubMedCrossRefGoogle Scholar
  234. van Driel IR, Wilks AF, Pietersz GA, Goding JW (1985) Murine plasma cell membrane antigen PC-1: Molecular cloning of cDNA and analysis of expression. Proc Natl Acad Sci USA 82: 8619–8623Google Scholar
  235. Vasconcelos EG, Ferreira ST, Carvalho TMU, de Souza W, Kettlun AM, Mancilla M, Valenzuela MA, Verjovski-Almeida S (1996) Partial purification and immunohistochemical localization of ATP diphosphohydrolase from Schistosoma mansoni. Immunological cross-reactivities with potato apyrase and Toxoplasma gondii nucleoside triphosphate hydrolase. J Biol Chem 271: 22139–22145PubMedCrossRefGoogle Scholar
  236. Vigne P, Breittmayer JP, Frelin C (1998) Analysis of the influence of nucleotidases on the apparent activity of exogenous ATP and ADP at P2Y, receptors. Br J Pharmacol 125: 675–680PubMedCrossRefGoogle Scholar
  237. Wang TF, Guidotti G (1996) CD39 is an ecto-(Ca2+,Mg2+)-apyrase. J Biol Chem 271: 9898–9901PubMedCrossRefGoogle Scholar
  238. Wang TF, Rosenberg PA, Guidotti G (1997) Characterization of brain ecto-apyrase: evidence for only one ecto-apyrase (CD39) gene. Mol Brain Res 47: 295–302PubMedCrossRefGoogle Scholar
  239. Wang TF, Guidotti G (1998a) Golgi localization and functional expression of human uridine diphosphatase. J Biol Chem 273: 11392–11399PubMedCrossRefGoogle Scholar
  240. Wang TF, Guidotti G (1998b) Widespread expression of ecto-apyrase (CD39) in the central nervous system. Brain Res 790: 318–322PubMedCrossRefGoogle Scholar
  241. Wang TF, Ou Y, Guidotti G (1998) The transmembrane domains of ectoapyrase (CD39) affect its enzymatic activity and quaternary structure. J Biol Chem 273: 24814–24821PubMedCrossRefGoogle Scholar
  242. Welford LA, Cusack NJ, Hourani MO (1986) ATP analogues and the guinea-pig taenia coli: A comparison of the structure-activity relationships of ectonucleotidases with those of the P2-purinoceptor. Eur J Pharmacol 129: 217–224PubMedCrossRefGoogle Scholar
  243. Welford LA, Cusack NJ, Hourani SMO (1987) The structure-activity relationships of ectonucleotidases and the excitatory P2-purinoceptors: Evidence that dephosphorylation of ATP analogues reduces pharmacological potency. Eur J Pharmacol 141: 123–130Google Scholar
  244. Whyte PP (1996) Hypophosphatasia: natures window on alkaline phosphatase function in man. In: Bilezkian J, Raisz L, Rodan G (eds) Principles of bone biology. Academic Press, San Diego, pp 951–968Google Scholar
  245. Wiendl HS, Schneider C, Ogilvie A (1998) Nucleotide metabolizing ectoenzymes are upregulated in A431 cells periodically treated with cytostatic ATP leading to partial resistance without preventing apoptosis. Biochim Biophys Acta (Mol Cell Res) 1404: 282–298CrossRefGoogle Scholar
  246. Wieraszko A, Ehrlich YH (1994) On the role of extracellular ATP in the induction of long-term potentiation in the hippocampus. J Neurochem 63: 1731–1738PubMedCrossRefGoogle Scholar
  247. Wittenburg H, Bultmann R, Pause B, Ganter C, Kurz G, Starke K (1996) P2-purinoceptor antagonists: II. Blockade of P2-purinoceptor subtypes and ecto-nucleotidases by compounds related to Evans blue and trypan blue. Naunyn Schmiedebergs Arch Pharmacol 354: 491–497PubMedCrossRefGoogle Scholar
  248. Ziganshin AU, Hoyle CHV, Burnstock G (1994a) Ecto-enzymes and metabolism of extracellular ATP. Drug Develop Res 32: 134–146CrossRefGoogle Scholar
  249. Ziganshin AU, Hoyle CHV, Ziganshina LE, Burnstock G (1994b) Effects of cyclopiazonic acid on contractility and ecto- ATPase activity in guinea-pig urinary bladder and vas deferens. Br J Pharmacol 113: 669–674PubMedCrossRefGoogle Scholar
  250. Ziganshin AU, Ziganshina LE, Bodin P, Bailey D, Burnstock G (1995a) Effects of P2purinoceptor antagonists on ecto-nucleotidase activity of guinea-pig vas deferens cultured smooth muscle cells. Biochem Mol Biol Int 36: 863–869PubMedGoogle Scholar
  251. Ziganshin AU, Berdnikov EA, Ziganshina LE,Tantasheva FR, Hoyle CHV, Burnstock G (1995b) Effects of a,ß-unsaturated sulphones and phosphonium salts on ectoATPase activity and contractile responses mediated via P2x-purinoceptors. Gen Pharmacol 26: 527–532Google Scholar
  252. Ziganshin AU, Ziganshina LE, Hoyle CHV, Burnstock G (1995c) Effects of divalent cations and La’ on contractility and ecto- ATPase activity in the guinea-pig urinary bladder. Br J Pharmacol 114: 632–639PubMedCrossRefGoogle Scholar
  253. Ziganshin AU, Ziganshina LE, King BF, Pintor J, Burnstock G (1996) Effects of P2-purinoceptor antagonists on degradation of adenine nucleotides by ectonucleotidases in folliculated oocytes of Xenopus laevis. Biochem Pharmacol 51: 897–901PubMedCrossRefGoogle Scholar
  254. Zimmermann H (1992) 5’-Nucleotidase: molecular structure and functional aspects. Biochem J 285:345–365Google Scholar
  255. Zimmermann H (1994) Signalling via ATP in the nervous system. Trends Neurosci 17: 420–426PubMedCrossRefGoogle Scholar
  256. Zimmermann H (1996a) Biochemistry, localization and functional roles of ectonucleotidases in the nervous system. Prog Neurobiol 49: 589–618PubMedCrossRefGoogle Scholar
  257. Zimmermann H (1996b) Extracellular purine metabolism. Drug Develop Res 39: 337–352CrossRefGoogle Scholar
  258. Zimmermann H, Pearson J (1998) Extracellular metabolism of nucleotides and adenosine in the cardiovascular system. In: Burnstock G, Dobson JG, Liang BT, Linden J (eds) Cardiovascular biology of purines. Kluwer, London pp342358Google Scholar
  259. Zimmermann H (1999a) Two novel families of ecto-nucleotidases: Molecular structures, catalytic properties, and a search for function. Trends Pharmacol Sci 20: 231–236PubMedCrossRefGoogle Scholar
  260. Zimmermann H (1999b) Nucleotides and cd39: principal modulatory players in hemostasis and thrombosis. Nature Med 5: 987–988PubMedCrossRefGoogle Scholar
  261. Zimmermann H, Braun N (1999) Ecto-nucleotidases: molecular structures, catalytic properties, and functional roles in the nervous system. Prog Brain Res 120: 371–385PubMedCrossRefGoogle Scholar
  262. Zimmermann H, Beaudoin AR, Bollen M, Goding JW, Guidotti G, Kirley TL, Robson SC, Sano K (2000) Proposed nomenclature for two novel nucleotide hydrolyzing enzyme families expressed on the cell surface. In: Vanduffel L, Lemmens R (eds) Ecto-ATPases and related ectonucleotidases, Shaker Publishing BV, Maastricht, pp 1–8Google Scholar

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© Springer-Verlag Berlin Heidelberg 2001

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  • H. Zimmermann

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