Enzymatic Characteristics and Possible Role of Synaptosomal Ecto-Adenosine Triphosphatase from Mammalian Brain

  • Agnes Nagy
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)


In 1957 Engelhardt described a very active ATPase enzyme on the outer surface of avian (nucleated) red blood cells. He stated that the action of this enzyme is strictly oriented in space towards the surrounding medium: it splits rapidly any ATP that reaches the outside of the cell and leaves the ATP on the inside of the cell unaffected. He clearly distinguished this specific cell surface “ecto-enzyme” from “exo-enzymes” which are secreted into the extracellular space and also from the normal “endo-enzymes” which act within the cell. Prior to the observations of Engelhardt, a fairly active cell surface ATPase had already been reported by Acs et al. (1954) in ascites tumour cells. A detailed analysis of the Ehrlich ascites tumour cell surface ecto-ATPase was later carried out by Ronquist and Agren (1975).


ATPase Activity Nerve Ending Adenylate Kinase Adenosine Triphosphatase Enzymatic Characteristic 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acs G, Ostrowski W, Straub FB (1954) Über die Adenylpyrophosphatase-aktivität an der Ober-fläche der Aszites-Krebszellen. Acta Physiol Acad Sci Hung 6: 260–263Google Scholar
  2. Agren G, Ponten J, Ronquist G, Westermark B (1971) Demonstration of an ATPase at the cell surface of intact normal and neoplastic tumour cells in culture. J Cell Physiol 78: 171–176PubMedCrossRefGoogle Scholar
  3. Agren G, Ponten J, Ronquist G, Westermark B (1976) Comparison between Ca2+ and Mg2+ on surface located ATPase of intact normal and neoplastic human cells in culture. Acta Physiol Scand 98: 263–265PubMedCrossRefGoogle Scholar
  4. Amende LM, Chock SP, Albers RW (1983) Characterization of the Ca2+- and Mg2+-dependent ATPases in Electrophorus electroplax microsomes. J Neurochem 40: 1040–1047PubMedCrossRefGoogle Scholar
  5. Berne RM, Rall TW, Rubio R (eds; 1983 ) Regulatory function of adenosine. Nijhoff, The Hague Boston, LondonGoogle Scholar
  6. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24: 509–581PubMedGoogle Scholar
  7. Burnstock G (1975) Purinergic transmission. In: Iversen LL, Iversen SD, Snyder SH (eds), vol 5. Plenum, New York, pp 131–194Google Scholar
  8. Carraway CAC, Corrado FJ IV, Fogle DD, Carraway KL (1980) Ecto-enzymes of mammary gland and its tumours. Biochem J 191: 45–51PubMedGoogle Scholar
  9. Carraway KL, Fogle DD, Chesnut RW, Huggins JW, Carraway CAC (1976) Ecto-enzymes of mammary gland and its tumours. J Biol Chem 251: 6173–6178PubMedGoogle Scholar
  10. Chambers DA, Salzman EW, Neri LL (1967) Characterization of “ecto-ATPase” of human blood platelets. Arch Biochem Biophys 119: 173–178PubMedCrossRefGoogle Scholar
  11. Coetzee GA, Gevers W (1977) 5-bromo-2/-deoxyuridine-stimulated calcium ion- or magnesium ion-dependent ecto-(adenosine triphosphatase) activity of cultured hamster cardiac cells. Biochem J 1964: 645–652Google Scholar
  12. Da Prada M, Pletscher A (1968) Isolated 5′-hydroxy tryptamine organelles of rabbit blood platelets:physiological properties and drug-induced changes. Br J Pharmacol 34: 591–597PubMedGoogle Scholar
  13. De Mey J, Burnstock G, Vanhoutte PM (1979) Modulation of the evoked release of noradrenaline in canine saphenous vein via presynaptic receptors for adenine but not ATP. Eur J Pharmacol 55: 401–405PubMedCrossRefGoogle Scholar
  14. De Pierre JW, Karnowsky ML (1974a) Ecto-enzymes of the guinea pig polymorphonuclear leukocyte I. Evidence for an ecto-adenosine monophosphatase, -adenosine triphosphatase, and -p-nitrophenyl phosphatase. J Biol Chem 249: 7111–7120Google Scholar
  15. De Pierre JW, Karnowsky ML (1974b) Ecto-enzymes of the guinea pig polymorphonuclear leukocyte II. Properties and suitability as markers for the plasma membrane. J Biol Chem 249: 7121–7129Google Scholar
  16. Desaiah D, Ho IK (1977) Kinetics of catecholamine sensitive Na+K+-ATPase activity in mouse brain synaptosomes. Biochem Parmacol 26: 2029–2035CrossRefGoogle Scholar
  17. Dowdall MJ (1977) Adenine nucleotides in cholinergic transmission: presynaptic aspects. In: Nucleotides and neurotransmission. Conf Neurobiol de Gif, Dec 1977, pp 7–8Google Scholar
  18. Dunwiddie TV (1980) Endogenously released adenosine regulates excitability in the in vitrohippocampus. Epilepsia 21: 541–548PubMedCrossRefGoogle Scholar
  19. Engelhardt WA (1957) Enzymes as structural elements of physiological mechanisms. Proc Int Symp Enzym Chem (Tokyo) 2: 163–166Google Scholar
  20. Geffen LB, Livett BG (1971) Synaptic vesicles in sympathetic neurons. Physiol Rev 51: 98–157PubMedGoogle Scholar
  21. Hamlyn JM, Senior AE (1983) Evidence that Mg2+- or Ca2+-activated adenosine triphosphatase in rat pancreas is a plasma-membrane ecto-enzyme. Biochem J 214: 59–68PubMedGoogle Scholar
  22. Hedquist P, Fredholm BB (1976) Effects of adenosine on adrenergic neurotransmission. Prejunctional inhibition and postjunctional enhancement. Naunyn-Schmiedebergs Arch Pharmacol 293: 217–223CrossRefGoogle Scholar
  23. Israel M, Meunier FM (1978) The release of ATP triggered by transmitter action and its possible physiological significance: retrograde transmission. J Physiol (Paris) 74: 485–490Google Scholar
  24. Israel M, Lesbats B, Manaranche R, Meurier FM, Franchon P (1980) Retrograde inhibition of transmitter release by ATP. J Neurochem 34: 923–932PubMedCrossRefGoogle Scholar
  25. Javors MA, Bowden CL, Ross DH (1981) Kinetic characterization of Ca2+ transport in synaptic membranes. J Neurochem 37: 381–387PubMedCrossRefGoogle Scholar
  26. Katz B (1969) The release of neural transmitter substances. Liverpool University Press, LiverpoolGoogle Scholar
  27. Keller F, Zimmermann H (1983) Ecto-adenosine triphosphatase activity at the cholinergic nerve endings of the Torpedo electric organ. Life Sci 33: 2635–2641PubMedCrossRefGoogle Scholar
  28. Khoo JC, Russel PJ (1982) Isoenzymes of adenylate kinase in human tissue. Biochem Biophys Acta 268: 98–101Google Scholar
  29. Kuroda Y (1978) Physiological roles of adenosine derivatives which are released during neuro-transmission in mammalian brain. J Physiol (Paris) 74: 463–470Google Scholar
  30. Lagerkrantz H (1971) Isolation and characterization of sympathetic nerve trunk vesicles. Acta Physiol Scand Suppl 366: 1–44Google Scholar
  31. Majumder GC (1981) Enzymic characters of ecto-adenosine triphosphatase in rat epididymal intact spermatozoa. Biochem J 195: 110–118Google Scholar
  32. Majumder GC, Biswas R (1979) Evidence for the occurence of an ecto-(adenosine triphosphatase) in rat epididymal spermatozoa. Biochem J 183: 737–743PubMedGoogle Scholar
  33. McAfee DA, Greengard P (1972) Adenosine 3′-5′-monophosphate electrophysiological evidence for a role in synaptic transmission. Science (Wash DC) 178: 310–312Google Scholar
  34. Medzihradsky F, Cullen EI, Lin HL, Bole GG (1980) Drug-sensitive ecto-ATPase in human leukocytes. Biochem Pharmacol 29: 2285–2290PubMedCrossRefGoogle Scholar
  35. Meyer EM, Cooper JR (1981) Correlation between Na+K+-ATPase activity and acetylcholine release in rat cortical synaptosomes. J Neurochem 36: 467–475PubMedCrossRefGoogle Scholar
  36. Nagy A, Rosenberg MD (1981) Adenosine triphosphatase activity at the external surface of synaptosomes. 8th Meet Int Soc Neurochem, Nottingham, p 114Google Scholar
  37. Nagy A, Baker RR, Morris SJ, Whittaker VP (1976) The preparation and characterization of synaptic vesicles of high purity. Brain Res 109: 285–309PubMedCrossRefGoogle Scholar
  38. Nagy A, Escueta AV (1984) Rapid preparation of synaptosomes from mammalian brain using non-toxic isoosmotic gradient material (Percoll). J Neurochem 43: 1114–1123PubMedCrossRefGoogle Scholar
  39. Nagy A, Shuster TA, Rosenberg MD (1983) Adenosine triphosphatase activity at the external surface of chicken brain synaptosomes. J Neurochem 40: 226–232PubMedCrossRefGoogle Scholar
  40. Phyllis JW, Kostopoulos GK, Limacher JJ (1974) Depression of corticospinal cells by various purines and pyrimidines. Can J Physiol Pharmacol 52: 1226–1229CrossRefGoogle Scholar
  41. Pradhan TK, Criss WE (1976) The major forms of adenylate kinase from adult and fetal rat tissues. Enzyme (Basel) 21: 327–331Google Scholar
  42. Reddington M, Mehl E (1979) Synaptic membrane proteins as substrates for cyclic AMP-stim- ulated protein phosphorylation in various regions of rat brain. Biochim Biophys Acta 555: 230–238PubMedCrossRefGoogle Scholar
  43. Ronquist G, Agren GK (1975) A Mg2+- and Ca2+-stimulated adenosine triphosphatase at the outer surface of Erlich ascites tumour cells. Cancer Res 35: 1402–1406PubMedGoogle Scholar
  44. Rosenblatt DE, Lauter CJ, Trams EG (1976) Deficiency of a Ca2+-ATPase in brains of seizure prone mice. J Neurochem 27: 1299–1304PubMedCrossRefGoogle Scholar
  45. Schubert P, Mitzdorf U (1979) Analysis and quantitative evaluation of the depressive effect of adenosine on evoked potentials in the hippocampal slice. Brain Res 172: 186–190PubMedCrossRefGoogle Scholar
  46. Schubert P, Lee K, Kreutzberg GW (1981) Formation and function of adenosine in the CNS I.Release and modulatory action. 8th Meet Int. Soc Neurochem, Nottingham, p111Google Scholar
  47. Schwabe U, Ebert R, Erbler HC (1973) Adenosine release from isolated fat cells and its significance for the effect of hormones on 3′,5′-AMP levels and lipolysis. Naunyn-Schmiede- bergs Arch Pharmacol 276: 133–148CrossRefGoogle Scholar
  48. Schwartz A, Lindenmayer GE, Allen JC (1975) The sodium-potassium adenosine triphosphatase: pharmacological physiological and biochemical aspects. Pharmacol Rev 27: 3–134PubMedGoogle Scholar
  49. Skou JC (1957) The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta 23: 394–401PubMedCrossRefGoogle Scholar
  50. Smolen JE, Weissmann G (1978) Mg2+-ATPase as a membrane ecto-enzyme of human granulocytes. Inhibitors, activators and response to phagocytosis. Biochim Biophys Acta 512: 525–538PubMedCrossRefGoogle Scholar
  51. Sorensen RG, Mahler HR (1981) Calcium stimulated adenosine triphosphatase in synapticmembranes. J Neurochem 37: 1407–1418PubMedCrossRefGoogle Scholar
  52. Sorensen RG, Mahler HR (1982) Localization of endogenous ATPase at the nerve terminal. J Bioenerg Biomembr 14: 527–547PubMedCrossRefGoogle Scholar
  53. Stefanovic V, Ciesielski-Treska J, Ebel A, Mandel P (1974a) Nucleoside triphosphatase activity at the external surface of neuroblastoma cells. Brain Res 81: 427–441PubMedCrossRefGoogle Scholar
  54. Stefanovic V, Ciesielski-Treska J, Ebel A, Mandel P (1974b) Ca2+-activated ATPase at the external surface of neuroblastoma cells in culture. FEBS Lett 49: 43–46PubMedCrossRefGoogle Scholar
  55. Stefanovic V, Ledig M, Mandel P (1976a) Divalent cation activated ecto-nucleoside triphosphatase activity of nervous system cells in tissue culture. J Neurochem 27: 799–805PubMedCrossRefGoogle Scholar
  56. Stefanovic V, Mandel P, Rosenberg A (1976b) Ecto-5′-nucleotidase of intact cultured Cc rat glioma cells. J Biol Chem 251: 3900–3905PubMedGoogle Scholar
  57. Stone TW (1981) Physiological roles for adenosine and adenosine 5′-triphosphatase in the neuron system. Neuroscience 6: 523–555PubMedCrossRefGoogle Scholar
  58. Stone TW, Taylor DA (1977) Microiontophoretic studies of the effects of cyclic nucleotides on excitability of neurons in rat cerebral cortex. J Physiol (Lond) 266: 523–543Google Scholar
  59. Tada M, Yamada M, Ohmori F, Kuzuya T, Abe H (1979) In: Mukohata Y, Parker L (eds) Cation flux across biomembranes. Academic, London, pp 179–190Google Scholar
  60. Therien HM, Mushinski WE (1979) Distribution and properties of protein kinase and protein phosphatase activities in synaptosomal plasma membranes and synaptic junctions. Biochim Biophys Acta 585: 188–200PubMedCrossRefGoogle Scholar
  61. Tower DB (1960) In: Thomas J (ed) Neurochemistry of epilepsy, Thomas CC, Springfield, USAGoogle Scholar
  62. Trams EG (1974) Evidence for ATP action on the cell surface. Nature (Lond) 252:480–482CrossRefGoogle Scholar
  63. Trams EG, Lauter CJ (1974) On the sidedness of plasma membrane enzymes. Biochim Biophys Acta 345: 180–197PubMedCrossRefGoogle Scholar
  64. Trams EG, Lauter CJ (1978) Ecto-ATPase deficiency in glia of seizure-prone mice. Nature (Lond) 271: 270–271CrossRefGoogle Scholar
  65. Wang TY, Hussey CB, Sasse EA, Hause LL (1977) Platelet aggregation and the ouabain-insensitive ATPase. Ecto-ATPase, reflection of membrane integrity. Am J Clin Pathol 67: 528–532Google Scholar
  66. Weiss B, Sachs L (1977) Differences in surface membrane ecto-ATPase and ecto-AMPase in normal and malignant cells I. Decrease in ecto-ATPase in myeloid leukemic cells and the independent regulation of ecto-ATPase and ecto-AMPase. J Cell Physiol 93: 183–188PubMedCrossRefGoogle Scholar
  67. White TD (1978) Release of ATP from a synaptosomal preparation by elevated extracellular potassium and by veratridine. J Neurochem 30: 329–336PubMedCrossRefGoogle Scholar
  68. Whittaker VP, Essmann WE, Dowe GHC (1972) The isolation of pure cholinergic synaptic vesicles from the electric organs of elasmobranch fish of the family Torpedinidae. Biochem J 128: 833 - 846PubMedGoogle Scholar
  69. Wilson PD, Rustin GJ, Smith GP, Peters TJ (1981) Electron microscopic cytochemical localization of nucleoside phosphatases in normal and chronic granulocytic leukemic human neutro- phyls. Histochem 13: 73–84CrossRefGoogle Scholar
  70. Zimmermann H, Dowdall MJ, Lane DA (1979) Purine salvage at the cholinergic nerve endings of the Torpedo electric organ: the central role of adenosine. Neuroscience 4: 979–993PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • Agnes Nagy
    • 1
  1. 1.Department of NeurologyReed Neurological Research Center UCLA Center for Health SciencesLos AngelesUSA

Personalised recommendations