Pflügers Archiv

, Volume 385, Issue 1, pp 45–50 | Cite as

Blocking action of intracellularly injected neuraminidase on central synapses in vivo

  • F. X. Hipp
  • W. Gielen
  • Margaret A. Davies
  • D. H. Hinzen
Excitable Tissues and Central Nervous Physiology


The effect of neuraminidase on synaptic transmission was studied at cholinergic and noncholinergic contacts in the buccal and cerebral ganglion of Aplysia. The amplitudes of monosynaptic unitary postsynaptic potentials generated by intracellular stimulation of identified presynaptic neurones were measured as indication for the efficacy of synaptic transmission. Neuraminidase was either intrasomatically injected into a presynaptic neurone, or the whole ganglion was incubated with the enzyme.

Intrasomatic injection of the enzyme resulted in complete failure of synaptic transmission. This effect occurred independently of the transmitter used. The synaptic failure was presynaptic in origin. The biophysical characteristics of an injected neurone, particularly the amplitude and propagation of its action potential, did not appear to be affected by neuraminidase. Synaptic transmission and biophysical membrane properties were unaffected by extracellular neuraminidase.

We conclude that the synaptic blockade is due to the enzyme's action inside the presynaptic nerve ending. It seems most likely that neuraminidase cleaves sialicacid-containing-compounds associated with the nerve terminal surface membrane, probably thus causing failure of transmitter release.

Key words

Neuraminidase Synaptic transmission failure Enzymatic microdissection 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Augustinsson, K.-B., Ekedahl, G.: The properties of neuraminidasetreated serum cholinesterase. Biochim. Biophys. Acta56, 392–393 (1962)Google Scholar
  2. Baux, G., Simonneau, M., Tauc, L.: Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates. J. Physiol. (Lond.)291, 161–178 (1979)Google Scholar
  3. Breckenridge, W. C., Gombos, G., Morgan, I. G.: The lipid composition of adult rat brain synaptosomal plasma membranes. Biochim. Biophys. Acta266, 696–707 (1972)Google Scholar
  4. Brodbeck, U., Gentinetta, R., Lundin, S. J.: Multiple forms of a cholinesterase from body muscle and possible role of sialic acid in cholinesterase reaction specificity. Acta Chem. Scand.27, 561–572 (1973)Google Scholar
  5. Brunngraber, E. G., Dekirmenjian, H., Brown, B. D.: The distribution of protein-bound N-acetylneuraminic acid in subcellular fractions of rat brain. Biochem. J.103, 73–78 (1967)Google Scholar
  6. Coggeshall, R. E., Kandel, E. R., Kupfermann, I., Waziri, R.: A morphological and functional study on a cluster of identifiable neurosecretory cells in the abdominal ganglion ofAplysia californica. J. Cell. Biol.31, 363–368 (1966)Google Scholar
  7. Dekirmenjian, H., Brunngraber, E. G.: Distribution of proteinbound N-acetylneuraminic acid in subcellular particulate fractions prepared from rat whole brain. Biochim. Biophys. Acta177, 1–10 (1969)Google Scholar
  8. Drzeniek, R.: Viral and bacterial neuraminidase. Curr. Top. Microbiol. Immunol.59, 35–74 (1972)Google Scholar
  9. Eichberg, J., Whittaker, V. P., Dawson, R. M. C.: The distribution of lipids in subcellular particles of guinea-pig brain. Biochem. J.92, 91–100 (1964)Google Scholar
  10. Gardner, D.: Bilateral symmetry and interneuronal organization in the buccal ganglion ofAplysia. Science173, 550–553 (1971)Google Scholar
  11. Heijlman, J., Roukema, P. A.: Action of calf brain sialidase on gangliosides, sialoglycoproteins and sialoglycopeptides. J. Neurochem.19, 2567–2575 (1972)Google Scholar
  12. Heilbronn, E.: Treatment of horse serum cholinesterase with sialidase. Acta Chem. Scand.16, 516 (1962)Google Scholar
  13. Heilbronn, E., Cedergren, E.: Chemically induced changes in the acetylcholine uptake and storage capacity of brain tissue. In: Conference on the effect of cholinergic mechanisms in the CNS (E. Heilbronn, A. Winter, eds.),pp. 245–269. Stockholm (Sweden): Skoklostu 1970Google Scholar
  14. Hinzen, D. H., Davies, M. A.: Synaptic connexions and related postsynaptic pharmacology studied in the cerebral ganglion ofAplysia. Brain Res.144, 49–62 (1978)Google Scholar
  15. Hughes, G. M., Tauc, L.: The path of giant cell axons inAplysia depilans. Nature191, 404–405 (1961)Google Scholar
  16. Lapetina, E. G., Soto, E. F., De Robertis, E.: Gangliosides and acetylcholinesterase in isolated membranes of rat brain cortex. Biochim. Biophys. Acta135, 33–43 (1967)Google Scholar
  17. Lapetina, E. G., Soto, E. F., De Robertis, E.: Lipids and Proteolipids in isolated subcellular membranes of rat brain cortex. J. Neurochem.15, 437–445 (1968)Google Scholar
  18. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951)Google Scholar
  19. Lüben, G., Sedlacek, H. H., Seiler, F. R.: Quantitative experiments on the cell membranes binding of neuraminidase. Behring Inst. Mitt.59, 30–37 (1976)Google Scholar
  20. Öhman, R.: Subcellular fraction of ganglioside sialidase from human brain. J. Neurochem.18, 89–95 (1971)Google Scholar
  21. Rahmann, H., Rösner, H., Breer, H.: A functional model of sialoglyco-macromolecules in synaptic transmission and memory function. J. Theor. Biol.57, 231–237 (1976)Google Scholar
  22. Schengrund, C.-L., Rosenberg, A.: Intracellular location and properties of bovine brain sialidase. J. Biol. Chem.245, 6196–6200 (1970)Google Scholar
  23. Schick, H. J., Zilg, H.: Production and quality control of therapeutically applicableVibrio cholerae neuraminidase (VCN). Dev. Biol. Stand.38, 81–85 (1978)Google Scholar
  24. Seminario, L. M., Hren, N., Gomez, C. J.: Lipid distribution in subcellular fractions of the rat brain. J. Neurochem.11, 197–207 (1964)Google Scholar
  25. Svensmark, O., Kristensen, P.: Electrophoretic mobility of sialidasetreated human serum cholinesterase. Dan. Med. Bull.9, 16–17 (1962)Google Scholar
  26. Tauc, L., Hinzen, D. H.: Neuraminidase: its effect on synaptic transmission. Brain Res.80, 340–344 (1974)Google Scholar
  27. Tettamanti, G., Morgan, I. G., Gombos, G., Vincendon, G., Mandel, P.: Subsynaptosomal localization of brain particulate neuraminidase. Brain Res.47, 515–518 (1972)Google Scholar
  28. Tettamanti, G., Preti, A., Lombardo, A., Bonali, F., Zambotti, V.: Parallelism of subcellular location of major particulate neuraminidase and gangliosides in rabbit brain cortex. Biochim. Biophys. Acta306, 466–477 (1973)Google Scholar
  29. Vaccari, A., Vertua, R., Furlani, A.: Decreased calcium uptake by rat fundal strips after pretreatment with neuraminidase or LSD in vitro. Biochem. Pharmacol.20, 2603–2612 (1971)Google Scholar
  30. Warren, L.: The thiobarbituric acid assay of sialic acids. J. Biol. Chem.234, 1971–1975 (1959)Google Scholar
  31. Whittaker, V. P.: Some properties of synaptic membranes isolated from the central nervous system. Ann. N. Y. Acad. Sci.137, 982–998 (1966)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • F. X. Hipp
    • 1
  • W. Gielen
    • 2
  • Margaret A. Davies
    • 1
  • D. H. Hinzen
    • 1
  1. 1.Institut für Normale und Pathologische PhysiologieUniversität zu KölnKöln 41Federal Republic of Germany
  2. 2.Pharmakologisches InstitutUniverität zu KölnKöln 41Federal Republic of Germany

Personalised recommendations