Clostridial Neurotoxins: Handling and Action at the Cellular and Molecular Level

  • E. Habermann
  • F. Dreyer
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 129)


Tetanus and botulism have fascinated mankind since they were first described by Hippocrates (cited by Major 1965) and Kerner (1817) respectively. Following the ascent of bacteriology at the end of the past century, the flow of research has been uninterrupted, and it may be safely stated that no other group of toxins has aroused as much interest as the clostridial neurotoxins. The pertinent literature presents not only a historical account of their handling by the scientific community, but also a cross-section of the development of science and the time-dependent ways of thinking and experimenting. The progress in understanding started with the detection of the causative bacteria and their toxins at the end of the 19th century, the period dominated by microbiology. A stage of macroscopic physiology ensued, resulting in the assignment of the intoxication to the spinal cord in tetanus and to the peripheral nerve endings in botulism. In parallel, the ascent of immunology led to the development of toxoids and antibodies and paved the way for treatment and prophylaxis of the diseases.


Botulinum Toxin Neuromuscular Junction Transmitter Release Botulinum Neurotoxin Tetanus Toxin 
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. Agui T, Syuto B, Oguma K, Iida H, Kubo S (1983) Binding of Clostridium botulinum type-C neurotoxin to rat brain synaptosomes. J Biochem 94:521–527PubMedGoogle Scholar
  2. Agui T, Syuto B, Oguma K, Iida H, Kubo S (1985) The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GT Ib ganglioside in Clostridium botulinum type-C neurotoxin. J Biochem 97:213–218PubMedGoogle Scholar
  3. Aktories K, Bärmann M, Ohishi I, Tsuyama S, Jakobs K, Habermann E (1986) Botulinum C2 toxin ADP-ribosylates actin. Nature (in press)Google Scholar
  4. Albus U, Habermann E (1983) Tetanus toxin inhibits the evoked outflow of an inhibitory (GABA) and an excitatory (D-aspartate) amino acid from particulate brain cortex. Toxicon 21:97–110PubMedGoogle Scholar
  5. Alouf JE, Fehrenbach FJ, Freer JH, Jeljaszewicz J (1984) Bacterial protein toxins. Academic, London, pp 13–78Google Scholar
  6. Alving CR, Iglewski BH, Urban KA, Moses J, Richards RL, Sadoff JC (1980) Binding of diphtheria toxin to phospholipids in liposomes. Proc Natl Acad Sci USA 77:1986–1990PubMedGoogle Scholar
  7. Ambache N, Morgan RS, Wright GP (1948 a) The action of tetanus toxin on the rabbit’s iris. J Physiol (Lond) 107:45–53Google Scholar
  8. Ambache N, Morgan RS, Wright GP (1948b) The action of tetanus toxin on the acetylcholine and choline esterase content of the rabbit’s iris. Br J Exp Path 29:408–418Google Scholar
  9. An der Lan B, Habig WH, Hardegree MC, Chrambach A (1980) Heterogeneity of I-125-labeled tetanus toxin in isoelectric focusing on Polyacrylamide gel and polyacrylamide-gel electrophoresis. Arch Biochem Biophys 200:206–215Google Scholar
  10. Ando S (1983) Gangliosides in the nervous system. Neurochem Int 5:507–537PubMedGoogle Scholar
  11. Anonymous (1975) Proceedings of the fourth international conference on tetanus, Dakar 1975 (2 vol). Fondation Merieux, Lyon, FranceGoogle Scholar
  12. Antony MT, Tonge DA (1980) Effects of denervation and botulinum toxin on muscle sensitivity to acetylcholine and acceptance of foreign innervation in the frog. J Physiol (Lond) 303:23–31Google Scholar
  13. Aquino DA, Bisby MA, Ledeen RW (1985) Retrograde axonal transport of gangliosides and glycoproteins in the motoneurons of rat sciatic nerve. J Neurochem 45:1262–1267PubMedGoogle Scholar
  14. Barrett EF, Stevens CF (1972) The kinetics of transmitter release at the frog neuromuscular junction. J Physiol (Lond) 227:691–708Google Scholar
  15. Bergey GK, Nelson PG, Macdonald RL, Habig WH (1981) Tetanus toxin produces blockade of synaptic transmission in mouse spinal cord neurons in culture. Soc Neurosci Abstr 7:439Google Scholar
  16. Bergey GK, Macdonald RL, Habig WH, Hardegree MC, Nelson PG (1983) Tetanus toxin: convulsant action on mouse spinal cord neurons in culture. J Neurosci 3:2310–2323PubMedGoogle Scholar
  17. Bergey GK, Bigalke H, Nelson PG (1986) Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action. J Neurophysiol (in press)Google Scholar
  18. Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321PubMedGoogle Scholar
  19. Bevan S, Wendon LMB (1984) A study of the action of tetanus toxin at rat soleus neuromuscular junctions. J Physiol (Lond) 348:1–17Google Scholar
  20. Bigalke H, Habermann E (1980) Blockade by tetanus and botulinum A toxin of postganglionic cholinergic nerve endings in the myenteric plexus. Naunyn Schmiedebergs Arch Pharmacol 312:255–263PubMedGoogle Scholar
  21. Bigalke H, Habermann E (1981) Botulinum A toxin inhibits the release of noradrenaline, acetylcholine, γ-aminobutyric acid and glycine from rat brain and spinal cord. IRCS Med Sci 9:105–106Google Scholar
  22. Bigalke H, Dimpfel W, Habermann E (1978) Suppression of 3H acetylcholine release from primary nerve cell cultures by tetanus and botulinum-A toxin. Naunyn Schmiedebergs Arch Pharmacol 303:133–138PubMedGoogle Scholar
  23. Bigalke H, Ahnert-Hilger G, Habermann E (1981a) Tetanus toxin and botulinum A toxin inhibit acetylcholine release from but not calcium uptake into brain tissue. Naunyn Schmiedebergs Arch Pharmacol 316:143–148PubMedGoogle Scholar
  24. Bigalke H, Heller I, Bizzini B, Habermann E (1981b) Tetanus toxin and botulinum A toxin inhibit release and uptake of various transmitters, as studied by particulate preparations from rat brain and spinal cord. Naunyn Schmiedebergs Arch Pharmacol 316:244–251PubMedGoogle Scholar
  25. Bigalke H, Dreyer F, Bergey GK (1985) Botulinum A neurotoxin inhibits non-cholinergic synaptic transmission in mouse spinal cord neurons in culture. Brain Res 360:318–324PubMedGoogle Scholar
  26. Bigalke H, Müller H, Dreyer F (1986) Botulinum A neurotoxin unlike tetanus toxin acts via a neuraminidase-sensitive structure. Toxicon (in press)Google Scholar
  27. Bizzini B (1977) Tetanus structure as a basis for elucidating its immunological and neuropharmacological activities. The specificity and action of animal, bacterial and plant toxins. In: Cuatrecasas P (ed) Receptors and recognition, Series B, vol I. Chapman and Hall, London, pp 177–218Google Scholar
  28. Bizzini B (1979) Tetanus toxin. Microbiol Rev 43:224–240PubMedGoogle Scholar
  29. Bizzini B (1984 a) Investigation of the mode of action of tetanus toxin with the aid of hybrid molecules consisting in part of tetanus toxin-derived fragments. In: Alouf JE, Fehrenbach FJ, Freer JH, Jeljaszewicz J (eds) Bacterial protein toxins. Academic, London, pp 427–434Google Scholar
  30. Bizzini B (1984b) Tetanus. In: Germanier R (ed) Bacterial vaccines. Academic, London, pp 37–68Google Scholar
  31. Bizzini B, Stoeckel K, Schwab M (1977) An antigenic polypeptide fragment isolated from tetanus toxin: chemical characterization, binding to gangliosides and retrograde axonal transport in various neuron systems. J Neurochem 28:529–542PubMedGoogle Scholar
  32. Bizzini B, Akert K, Glicksman M, Grob P (1980 a) Preparation of conjugates using two tetanus toxin-derived fragments: their binding to gangliosides and isolated synaptic membranes and their immunological properties. Toxicon 18:561–572PubMedGoogle Scholar
  33. Bizzini B, Grob P, Glicksman MA, Akert K (1980 b) Use of the B-IIb tetanus toxin-derived fragment as a specific neuropharmacological transport agent. Brain Res 193:221–227PubMedGoogle Scholar
  34. Bizzini B, Grob P, Akert K (1981) Papain-derived fragment IIC of tetanus toxin: its binding to isolated synaptic membranes and retrograde axonal transport. Brain Res 210:291–299PubMedGoogle Scholar
  35. Bóbr J, Guzek JW, Mach Z, Rembriesa R (1959) The behaviour of the endocrine system in the experimental tetanus. 1. Thyroid gland. Arch Immunol Terap Doswin (Pol) 7:171–176Google Scholar
  36. Boquet P, Duflot E (1982) Tetanus toxin fragment forms channels in lipid vesicles at low pH. Proc Natl Acad Sci USA 79:7614–7618PubMedGoogle Scholar
  37. Boquet P, Duflot E, Hauttecoeur B (1984) Low pH induces a hydrophobic domain in the tetanus toxin molecule. Eur J Biochem 144:339–344PubMedGoogle Scholar
  38. Borochov-Neori H, Yavin E, Montai M (1984) Tetanus toxin forms channels in planar lipid bilayers containing gangliosides. Biophys J 45:83–85PubMedGoogle Scholar
  39. Boroff DA, DasGupta BR (1971) Botulinum toxin. In: Kadis S et al. (eds) Microbiol toxins vol II A. Academic, New York, London, p 1–68Google Scholar
  40. Boroff DA, del Castillo J, Evoy WH, Steinhardt RA (1974) Observations on the action of type-A botulinum toxin on frog neuromuscular junctions. J Physiol 240:227–253PubMedGoogle Scholar
  41. Brenneman DE, Nelson PG (1985) Neuronal development in culture. Role of electrical activity. In: Bottenstein JE, Sato G (eds) Cell culture in the neurosciences. Plenum, New York, pp 289–316Google Scholar
  42. Brooks VB (1956) An intracellular study of the action of repetitive nerve volleys and of botulinum toxin on miniature end-plate potentials. J Physiol (Lond) 134:264–277Google Scholar
  43. Bülbring E (1946) Observations on the isolated phrenic nerve diaphragm preparation in the rat. Br J Pharmacol 1:38–61Google Scholar
  44. Burgen ASV, Dickens F, Zatman LJ (1949) The action of botulinum toxin on the neuromuscular junction. J Physiol 109:10–24PubMedGoogle Scholar
  45. Büttner-Ennever JA, Grob P, Akert K (1981a) A trans-synaptic autoradiographic study of the pathways controlling the extraocular eye muscles, using 125I-B-IIb tetanus toxin fragment. Ann NY Acad Sci 374:157–170PubMedGoogle Scholar
  46. Büttner-Ennever JA, Grob P, Akert K, Bizzini B (1981b) Trans-synaptic retrograde labeling in the oculomotor system of the monkey with 125I tetanus toxin BIIb fragment. Neurosci Lett 26:233–238PubMedGoogle Scholar
  47. Cabiaux V, Lorge P, Vandenbranden M, Falmagne O, Ruysschaert JM (1985) Tetanus toxin induces fusion and aggregation of lipid vesicles containing phosphatidylinositol at low pH. Biochem Biophys Res Comm 128:840–849PubMedGoogle Scholar
  48. Clowes AW, Cherry RJ, Chapman D (1972) Physical effects of tetanus toxin on model membranes containing ganglioside. J Mol Biol 67:49–57PubMedGoogle Scholar
  49. Collingridge GL, Davies J (1980) Tetanus toxin inhibits 3H GABA release from rat substantia nigra slices in vitro. J Physiol (Lond) 308:72P–73PGoogle Scholar
  50. Collingridge GL, Davies J (1982 a) Reversible effects of tetanus toxin on striatal-evoked responses and 3H-γ-aminobutyric acid release in the rat substantia nigra. Br J Pharmacol 76:403–411PubMedGoogle Scholar
  51. Collingridge GL, Davies J (1982 b) The in vitro inhibition of GABA release by tetanus toxin. Neuropharmacol 21:851–855Google Scholar
  52. Collingridge GL, Herron CE (1985) Effects of tetanus toxin on GABA synapses in the mammalian central nervous system. In: Nisticô et al. 7th Internatl Conf on Tetanus pp 127–142Google Scholar
  53. Collingridge GL, Davies J, James TA, Neal MJ, Tongroach P (1979) Effect of tetanus toxin on uptake and potassium-evoked release of radiolabeled transmitters from the substantia nigra and the striatum of the rat. J Physiol (Lond) 287:32P–33PGoogle Scholar
  54. Collingridge GL, Collins GGS, Davies J, James TA, Neal MJ, Tongroach P (1980) Effect of tetanus toxin on transmitter release from the substantia nigra and striatum in vitro. J Neurochem 34:540–547PubMedGoogle Scholar
  55. Collingridge GL, Thompson PA, Davies J, Mellanby J (1981) In vitro effect of tetanus toxin on GABA release from rat hippocampal slices. J Neurochem 37:1039–1041PubMedGoogle Scholar
  56. Colmeus C, Gomez S, Molgo J, Thesleff S (1982) Discrepancies between spontaneous and evoked synaptic potentials at normal, regenerating and botulinum toxin-poisoned mammalian neuromuscular junctions. Proc R Soc Lond [Biol] 215:63–74Google Scholar
  57. Critchley DR, Nelson PG, Habig WH, Fishman PH (1985) Fate of tetanus toxin bound to the surface of primary neurons in culture; evidence for rapid internalization. J Cell Biol 100:1499–1507PubMedGoogle Scholar
  58. Cull-Candy SG, Lundh H, Thesleff S (1976) Effect of botulinum toxin on neuromuscular transmission in the rat. J Physiol (Lond) 260:177–203Google Scholar
  59. Curtis DR, DeGroat WC (1968) Tetanus toxin and spinal inhibition. Brain Res 10:208–212PubMedGoogle Scholar
  60. Curtis DR, Felix D, Game CJA, McCulloch RM (1973) Tetanus toxin and the synaptic release of GABA. Brain Res 51:358–362PubMedGoogle Scholar
  61. DasGupta BR (1981) Structure and structure-function relation of botulinum neurotoxins. In: Lewis GE (ed) Biomedical aspects of botulism. Academic, New York, pp 1–19Google Scholar
  62. DasGupta BR, Sugiyama H (1972) Isolation and characterization of a protease from Clostridium botulinum type B. Biochim Biophys Acta 268:719–729PubMedGoogle Scholar
  63. DasGupta B, Woody MA (1984) Amino acid composition of Clostridium botulinum B toxin. Toxicon 22:312–315PubMedGoogle Scholar
  64. Datyner NB, Gage PW (1980) Phasic secretion of acetylcholine at a mammalian neuromuscular junction. J Physiol (Lond) 303:299–314Google Scholar
  65. Diamond J, Mellanby J (1971) The effect of tetanus toxin in the goldfish. J Physiol (Lond) 215:727–741Google Scholar
  66. Di Mari SJ, Cumming MA, Hash JH, Robinson JP (1982 a) Purification of tetanus toxin and its peptide components by preparative Polyacrylamide gel electrophoresis. Arch Biochem Biophys 214:342–353Google Scholar
  67. Di Mari SJ, Hash JH, Robinson JP (1982b) Characterization of tetanus toxins and toxin components by amino terminal analyses. Arch Biochem Biophys 214:354–365Google Scholar
  68. Dimpfel W, Habermann E (1977) Binding characteristics of 125I-labeled tetanus toxin to primary tissue cultures from mouse embryonic CNS. J Neurochem 29:1111–1120PubMedGoogle Scholar
  69. Dimpfel W, Neale JH, Habermann E (1975) 125I-labeled tetanus toxin as a neuronal marker in tissue cultures derived from embryonic CNS. Naunyn Schmiedebergs Arch Pharmacol 290:329–333PubMedGoogle Scholar
  70. Dimpfel W, Huang RTC, Habermann E (1977) Gangliosides in nervous tissue cultures and binding of 125I-labeled tetanus toxin, a neuronal marker. J Neurochem 29:329–334PubMedGoogle Scholar
  71. Dolezal V, Vyskocil F, Tucek S (1983) Decrease of the spontaneous non-quantal release of acetylcholine from the phrenic nerve in botulinum-poisoned rat diaphragm. Pflügers Arch 397:319–322PubMedGoogle Scholar
  72. Dolly JO, Black J, Williams RS, Melling J (1984a) Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization. Nature 307:457–460PubMedGoogle Scholar
  73. Dolly JO, Halliwell JV, Black JD, Williams RS, Pelchen-Matthews A, Breeze AL, Mehraban F, Othman IB, Black AR (1984 b) Botulinum neurotoxin and dendrotoxin as probes for studies on neurotransmitter release. J Physiol (Paris) 79:280–303Google Scholar
  74. Donovan JJ, Middlebrook JL (1985) Ion-conducting channels produced by botulinum neurotoxin in planar lipid membranes. Toxicon 23:560Google Scholar
  75. Donovan JJ, Simon MI, Montai M (1982) Insertion of diphtheria toxin into and across membranes. Role of phosphoinositide asymmetry. Nature 298:669–672PubMedGoogle Scholar
  76. Dreyer F, Schmitt A (1981) Different effects of botulinum A toxin and tetanus toxin on the transmitter-releasing process at the mammalian neuromuscular junction. Neurosci Lett 26:307–311PubMedGoogle Scholar
  77. Dreyer F, Schmitt A (1983) Transmitter release in tetanus and botulinum A toxin-poisoned mammalian motor end-plates and its dependence on nerve stimulation and temperature. Pflügers Arch 399:228–234PubMedGoogle Scholar
  78. Dreyer F, Mallart A, Brigant JL (1983) Botulinum A toxin and tetanus toxin do not affect presynaptic membrane currents in mammalian motor nerve endings. Brain Res 270:373–375PubMedGoogle Scholar
  79. Dreyer F, Becker C, Bigalke H, Funk J, Penner R, Rosenberg F, Ziegler M (1984) Action of botulinum A toxin and tetanus toxin on synaptic transmission. J Physiol (Paris) 79:252–258Google Scholar
  80. Duchen LW (1970) Changes in motor innervation and Cholinesterase localization induced by botulinum toxin in skeletal muscle of the mouse: differences between fast and slow muscles. J Neurol Neurosurg Psychiatry 33:40–54PubMedGoogle Scholar
  81. Duchen LW (1971) An electron-microscopic study of the changes induced by botulinum toxin in the motor end-plates of slow and fast skeletal muscle fibres of the mouse. J Neurol Sci 14:47–60PubMedGoogle Scholar
  82. Duchen LW, Strich SJ (1968) The effects of botulinum toxin on the pattern of innervation of skeletal muscle in the mouse. Q J Exp Physiol 53:84–89Google Scholar
  83. Duchen LW, Tonge DA (1973) The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor end-plates in slow and fast skeletal muscle of the mouse. J Physiol (Lond) 228:157–172Google Scholar
  84. Duda JJ, Slack JM (1969) Toxin production in Clostridium botulinum as demonstrated by electron microscopy. J Bacteriol 97:900–904PubMedGoogle Scholar
  85. Dudel J (1983) Transmitter release triggered by a local depolarization in motor nerve terminals of the frog: role of calcium entry and of depolarization. Neurosci Lett 41:133–138PubMedGoogle Scholar
  86. Duff JT, Wright GG, Yarinsky A (1956) Activation of Clostridium botulinum type E by trypsin. J Bacteriol 72:455–460Google Scholar
  87. Dumas M, Schwab ME, Thoenen H (1979 a) Retrograde axonal transport of specific macromolecules as a tool for characterizing nerve terminal membranes. J Neurobiol 10:179–197PubMedGoogle Scholar
  88. Dumas M, Schwab ME, Baumann R, Thoenen H (1979 b) Retrograde transport of tetanus toxin through a chain of 2 neurons. Brain Res 165:354–357PubMedGoogle Scholar
  89. Eisenbarth GS, Shimizu K, Bowring MA, Wells S (1982) Expression of receptors for tetanus toxin and monoclonal antibody A2B5 by pancreatic islet cells. Proc Natl Acad Sci USA 79:5066–5070PubMedGoogle Scholar
  90. Eklund MW, Poysky FT (1981) Relationship of bacteriophages to the toxigenicity of Clostridium botulinum and closely related organisms. In: Lewis GE (ed) Biomedical aspects of botulism. Academic, New York, pp 93–107Google Scholar
  91. Eklund MW, Poysky FT, Boatman ES (1969) Bacteriophages of Clostridium botulinum types A, B, E and F and nontoxigenic strains resembling type E. J Virol 3:270–274PubMedGoogle Scholar
  92. Erdmann G, Habermann E (1977) Histoautoradiography of central nervous system in rats with generalized tetanus due to 125I-toxin. Naunyn Schmiedebergs Arch Pharmacol 301:135–138PubMedGoogle Scholar
  93. Erdmann G, Hanauske A, Wellhöner HH (1981) Intraspinal distribution and reaction in the grey matter with tetanus toxin of intracisternally injected anti-tetanus toxoid F(ab)2 fragments. Brain Res 211:367–377PubMedGoogle Scholar
  94. Fabian R, Coulter JD (1985) Transneuronal transport of lectins. Brain Res 344:41–48PubMedGoogle Scholar
  95. Fairweather NF, Lyness VA, Pickard DJ, Allen GF, Thomson RO (1986) Cloning, nucleotide sequencing, and expression of tetanus toxin fragment C in Escherichia coli. J Bacteriol 165:21–27PubMedGoogle Scholar
  96. Fedinec AA, Shank RP (1971) Effect of tetanus toxin on the content of glycine, gamma-aminobutyric acid, glutamate, glutamine and aspartate in the rat spinal cord. J Neurochem 18:2229–2234PubMedGoogle Scholar
  97. Filiogmeni B, Grasso A (1985) Tetanus toxin affects the K+-stimulated release of catecholamines from nerve growth factor-treated PC 12 cells. Biochem Biophys Res Comm 128:249–256Google Scholar
  98. Fillenz M, Gagnon C, Stoeckel K, Thoenen H (1976) Selective uptake and retrograde axonal transport of dopamine-β-hydroxylase antibodies in peripheral adrenergic neurons. Brain Res 114:293–303PubMedGoogle Scholar
  99. Finn CW, Silver RP, Habig WH, Hardegree MC, Zon G, Garon CF (1984) The structural gene of tetanus neurotoxin is on a plasmid. Science 224:881–884PubMedGoogle Scholar
  100. Focá A, Rotiroti D, Mastroeni P, Nistico G (1984) Effects of tetanus toxin after intracerebral microinjection are antagonised by drugs enhancing GABAergic transmission in adult fowls. Neuropharmacology 23:155–158PubMedGoogle Scholar
  101. Gähwiler BH (1984) Slice cultures of cerebellar, hippocampal and hypothalamic tissue. Experientia 40:235–244PubMedGoogle Scholar
  102. Gammon CM, Ledeen RW (1985) Evidence for the presence of a ganglioside transfer protein in brain. J Neurochem 44:979–984PubMedGoogle Scholar
  103. Goldberg RL, Costa T, Habig WH, Kohn LD, Hardegree MC (1981) Characterization of fragment C and tetanus toxin binding to rat brain membranes. Mol Pharmacol 20:565–570PubMedGoogle Scholar
  104. Gonatas NK, Harper C, Mizutani T, Gonatas JO (1979) Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport. J Histochem Cytochem 27:728–734PubMedGoogle Scholar
  105. Goretzki K, Habermann E (1985) Enzymatic hydrolysis of tetanus toxin by intrinsic and extrinsic proteases. Characterization of the fragments by monoclonal antibodies. Med Microbiol Immunol 174:139–150PubMedGoogle Scholar
  106. Gundersen CB (1980) The effects of botulinum toxin on the synthesis, storage and release of acetylcholine. Progr Neurobiol 14:99–119Google Scholar
  107. Gundersen CB Jr, Howard BD (1978) The effects of botulinum toxin on acetylcholine metabolism in mouse brain slices and synaptosomes. J Neurochem 31:1005–1013PubMedGoogle Scholar
  108. Gundersen CB, Jenden DJ (1983) Spontaneous output of acetylcholine from rat diaphragm preparations declines after treatment with botulinum toxin. J Pharmacol Exp Ther 224:265–268PubMedGoogle Scholar
  109. Gundersen CB, Katz B, Miledi R (1982) The antagonism between botulinum toxin and calcium in motor nerve terminals. Proc R Soc Lond B 216:369–376PubMedGoogle Scholar
  110. Habermann E (1970) Pharmakokinetische Besonderheiten des Tetanustoxins und ihre Beziehung zur Pathogenese des lokalen bzw. generalisierten Tetanus. Naunyn Schmiedebergs Arch Pharmacol 267:1–19PubMedGoogle Scholar
  111. Habermann E (1972) Distribution of 125I-tetanus toxin and 125I-toxoid in rats with local tetanus, as influenced by antitoxin. Naunyn Schmiedebergs Arch Pharmacol 272:75–88PubMedGoogle Scholar
  112. Habermann E (1973 a) Discrimination between binding to CNS, toxicity and immunoreactivity of derivatives of tetanus toxin. Med Microbiol Immunol 159:89–100PubMedGoogle Scholar
  113. Habermann E (1973 b) Interaction of labelled tetanus toxin and toxoid with substructures of rat brain and spinal cord in vitro. Naunyn Schmiedebergs Arch Pharmacol 276:341–359PubMedGoogle Scholar
  114. Habermann E (1974) 125I-labeled neurotoxin from Clostridium botulinum A: preparation, binding to synaptosomes and ascent to the spinal cord. Naunyn Schmiedebergs Arch Pharmacol 281:47–56PubMedGoogle Scholar
  115. Habermann E (1976) Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors. Naunyn Schmiedebergs Arch Pharmacol 293:1–9PubMedGoogle Scholar
  116. Habermann E (1977) Transmembranal and intracellular transport of pharmacologically active proteins and polypeptides. Naunyn Schmiedebergs Arch Pharmacol 297:11–14Google Scholar
  117. Habermann E (1978) Tetanus. In: Vinken PJ, Bruyn GE (eds) Handbook of clinical neurology, vol 33. I. Infections of the nervous system. North-Holland, Amsterdam, pp 491–547Google Scholar
  118. Habermann E (1981a) Botulinum A and tetanus toxin — similar actions on transmitter systems in vitro. In: Lewis GE (ed) Biomedical aspects of botulinum. Academic, New York, pp 129–141Google Scholar
  119. Habermann E (1981 b) Tetanus toxin and botulinum A neurotoxin inhibit and at higher concentration enhance noradrenaline outflow from particulate brain cortex in batch. Naunyn Schmiedebergs Arch Pharmacol 318: 105–111PubMedGoogle Scholar
  120. Habermann E, Albus U (1986) Interaction between tetanus toxin and rabbit kidney: A comparison with rat brain preparations. J Neurochem 46:1219–1226PubMedGoogle Scholar
  121. Habermann E, Breithaupt H (1978) The crotoxin complex — an example of biochemical and pharmacological protein complementation. Toxicon 16:19–30PubMedGoogle Scholar
  122. Habermann E, Dimpfel W (1973) Distribution of 125I-tetanus toxin and 125I-toxoid in rats with generalized tetanus, as influenced by antitoxin. Naunyn Schmiedebergs Arch Pharmacol 176:327–340Google Scholar
  123. Habermann E, Erdmann G (1978) Pharmacokinetic and histoautoradiographic evidence for the intra-axonal movement of toxin in the pathogenesis of tetanus. Toxicon 16:611–623PubMedGoogle Scholar
  124. Habermann E, Goretzki K (1985) Monoclonal antibodies against tetanus toxin and toxoid. In: Macario AJL, Conway de Macario E (eds) Monoclonal antibodies against bacteria, vol I. Academic, New York, pp 191–204Google Scholar
  125. Habermann E, Heller I (1975) Direct evidence for the specific fixation of Cl. botulinum A neurotoxin to brain matter. Naunyn Schmiedebergs Arch Pharmacol 287:97–106PubMedGoogle Scholar
  126. Habermann E, Tayot JL (1985) Interaction of solid-phase gangliosides with tetanus toxin and tetanus toxoid. Toxicon 23:913–920PubMedGoogle Scholar
  127. Habermann E, Wellhöner HH, Räker KO (1977) Metabolic fate of 125I-tetanus toxin in the spinal cord of rats and cats with early local tetanus. Naunyn Schmiedebergs Arch Pharmacol 299:187–196PubMedGoogle Scholar
  128. Habermann E, Dreyer F, Bigalke H (1980) Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum A toxin. Naunyn Schmiedebergs Arch Pharmacol 311:33–40PubMedGoogle Scholar
  129. Habermann E, Bigalke H, Heller I (1981) Inhibition of synaptosomal choline uptake by tetanus and botulinum A toxin. Partial dissociation of fixation and effect of tetanus toxin. Naunyn Schmiedebergs Arch Pharmacol 316:135–142PubMedGoogle Scholar
  130. Habermann E, Goretzki K, Albus U (1985) Tetanus toxin: Its interaction with tissue constituents and monoclonal antibodies. In: Nisticó et al. 7th Internat Conf on Tetanus pp 179–193Google Scholar
  131. Habig WH, Grollman EF, Ledley FD, Meldolesi MF, Aloj SM, Hardegree C, Kohn LD (1978) Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with thyrotropin receptor defect and in vivo stimulation of thyroid function. Endocrinology 102:844–851PubMedGoogle Scholar
  132. Habig WH, Kenimer JG, Hardegree MC (1983) Retrograde axonal transport of tetanus toxin: toxin-mediated antibody transport. In: Lin TY (ed) Frontiers in biochemical studies of proteins and membranes. Elsevier, New York, pp 463–473Google Scholar
  133. Habig WH, Bigalke H, Bergey GK, Neale EA, Nelson PG (1986) Tetanus toxin in dissociated spinal cord cultures: long-term characterization of form and action. J Neurochem (in press)Google Scholar
  134. Hagenah R, Benecke R, Wiegand H (1977) Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia interneurones. Naunyn Schmiedebergs Arch Pharmacol 299:267–272PubMedGoogle Scholar
  135. Hara T, Matsuda M, Yoneda M (1977) Isolation and some properties of nontoxigenic derivatives of a strain of Clostridium tetani. Biken J 20:105–115PubMedGoogle Scholar
  136. Harper CG, Gonatas JO, Stieber A, Gonatas NK (1980) In vivo uptake of wheat germ agglutinin- horseradish peroxidase conjugates into neuronal GERL and lysosomes. Brain Res 188:465–472PubMedGoogle Scholar
  137. Harris AJ, Miledi R (1971) The effect of type-D botulinum toxin on frog neuromuscular junctions. J Physiol (Lond) 217:497–515Google Scholar
  138. Haynes BF, Shimizu K, Eisenbarth GS (1983) Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J Clin Invest 71:9–14PubMedGoogle Scholar
  139. Helting TB, Habig WH (1984) Structural relationship, toxicity, binding activity and immunogenicity of tetanus toxin fragments. In: Alouf JE, Fehrenbach FJ, Freer JH, Jeljaszewicz J (eds) Bacterial protein toxins. Academic, London, pp 413–420Google Scholar
  140. Helting TB, Zwisler O (1974) Enzymatic breakdown of tetanus toxin. Biochem Biophys Res Commun 57:1263–1270PubMedGoogle Scholar
  141. Helting TB, Zwisler O (1977) Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments. J Biol Chem 252:187–193PubMedGoogle Scholar
  142. Helting TB, Ronneberger HJ, Vollerthun R, Neubauer V (1978) Toxicity of papain-digested tetanus toxin, pathological effect of fragment B in the absence of spastic paralysis. J Biol Chem 253:125–129PubMedGoogle Scholar
  143. Helting TB, Parschat S, Engelhard H (1979) Structure of tetanus toxin — demonstration and separation of a specific enzyme converting intracellular tetanus toxin to the extracellular form. J Biol Chem 254:10728–10733PubMedGoogle Scholar
  144. Heyer EJ, Nowak LM, Macdonald RL (1981) Bicuculline: a convulsant with synaptic and nonsyn-aptic actions. Neurology (NY) 31:1381–1390Google Scholar
  145. Higashida H, Sugimoto N, Ozutsumi K, Miki N, Matsuda M (1983) Tetanus toxin: a rapid and selective blockade of calcium, but not sodium, component of action potentials in cultured neuroblastoma NIE-115 cells. Brain Res 279:363–368PubMedGoogle Scholar
  146. Hirokawa N, Kitamura M (1975) Localization of radioactive 125I-labelled botulinum toxin at the neuromuscular junction of mouse diaphragm. Naunyn Schmiedebergs Arch Pharmacol 287:107–110PubMedGoogle Scholar
  147. Hirokawa N, Kitamura M (1979) Binding of Clostridium botulinum neurotoxin to the presynaptic membrane in the central nervous system. J Cell Biol 81:43–49PubMedGoogle Scholar
  148. Hoch DH, Romero-Mira M, Ehrlich BE, Finkelstein A, Das Gupta BR, Simpson LL (1985) Channels formed by botulinum, tetanus and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes. Proc Natl Acad Sci USA 82:1692–1696PubMedGoogle Scholar
  149. Holmgren J, Elwing H, Fredman P, Svennerholm L (1980) Polystyrene-adsorbed gangliosides for investigation of the structure of the tetanus toxin receptor. Eur J Biochem 106:371–379PubMedGoogle Scholar
  150. Iida H, Oguma K (1981) Toxin production and phage in Clostridium botulinum types C and D. In: Lewis GE (ed) Biomedical aspects of botulism. Academic, New York, pp 109–120Google Scholar
  151. Inoue K, Iida H (1968) Bacteriophages of Clostridium botulinum. J Virol 2:537–540PubMedGoogle Scholar
  152. James TA, Collingridge GL (1979) Rapid behavioral and biochemical effects of tetanus toxin microinjected into the substantia nigra: a dual role for GABA? Neurosci Lett 11:205–208PubMedGoogle Scholar
  153. Janicki P, Habermann E (1983) Tetanus and botulinum toxins inhibit, and black widow spider venom stimulates the release of methionine-enkephalin-like material in vitro. J Neurochem 41:395–402PubMedGoogle Scholar
  154. Johnston GAR, Groat WC de, Curtis DR (1969) Tetanus toxin and amino acid levels in cat spinal cord. J Neurochem 16:797–800PubMedGoogle Scholar
  155. Kaeser HE, Saner A (1969) Tetanus toxin, a neuromuscular blocking agent. Nature 223:842PubMedGoogle Scholar
  156. Kao J, Drachman DB, Price DL (1976) Botulinum toxin: mechanism of presynaptic blockade. Science 193:1256–1258PubMedGoogle Scholar
  157. Kasai N, Yu RK (1983) The monoclonal antibody A2B5 is specific to gangliosides GQ1c. Brain Res 277:155–159PubMedGoogle Scholar
  158. Katz B, Miledi R (1977) Transmitter leakage from motor nerve endings. Proc R Soc Lond B 196:59–72PubMedGoogle Scholar
  159. Kemplay S, Cavanagh JB (1983) Effects of acrylamide and botulinum toxin on horseradish peroxidase labelling of trigeminal motor neurons in the rat. J Anat 137:477–482PubMedGoogle Scholar
  160. Kerner J (1817) Vergiftung durch verdorbene Würste. In: Tübinger Blätter für Naturwissenschaften und Arzneikunde, Band 3, Heft 1Google Scholar
  161. Kim YI, Lomo T, Lupa MT, Thesleff S (1984) Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin. J Physiol (Lond) 356:587–599Google Scholar
  162. Kitamura M (1976) Binding of botulinum neurotoxin to the synaptosome fraction of rat brain. Naunyn Schmiedebergs Arch Pharmacol 295:171–175PubMedGoogle Scholar
  163. Kitamura M, Iwamori M, Nagai Y (1980) Interaction between Clostridium botulinum neurotoxin and gangliosides. Biochim Biophys Acta 628:328–335PubMedGoogle Scholar
  164. Knight DE, Tonge DA, Baker PF (1985) Inhibition of exocytosis in bovine adrenal medullary cells by botulinum toxin type D. Nature 317:719–721PubMedGoogle Scholar
  165. Kozaki S (1979) Interaction of botulinum type A, B and E derivative toxins with synaptosomes of rat brain. Naunyn Schmiedebergs Arch Pharmacol 308:67–70PubMedGoogle Scholar
  166. Kozaki S, Sakaguchi G (1982) Binding to mouse brain synaptosomes of Clostridium botulinum type E derivative toxin before and after tryptic activation. Toxicon 20:841–846Google Scholar
  167. Kozaki S, Miyazaki S, Sakaguchi G (1977) Development of antitoxin with each of two complementary fragments of Clostridium botulinum type B derivative toxin. Infect Immun 18:761–766PubMedGoogle Scholar
  168. Kozaki S, Miyazaki S, Sakaguchi G (1978) Structure of Clostridium botulinum type B derivative toxin: inhibition with a fragment of toxin from binding to synaptosomal fraction. Jpn J Med Sci Biol 31:163–166PubMedGoogle Scholar
  169. Kozaki S, Togashi S, Sakaguchi G (1981) Separation of Clostridium botulinum type A derivative toxin into two fragments. Jpn J Med Sci Biol 34:61–68PubMedGoogle Scholar
  170. Kriebel ME, Llados F, Matteson DR (1976) Spontaneous subminiature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. J Physiol (Lond) 262:553–581Google Scholar
  171. Kristensson K, Olsson T (1978) Uptake and retrograde axonal transport of horseradish peroxidase in botulinum-intoxicated mice. Brain Res 155:118–123PubMedGoogle Scholar
  172. Kryzhanovsky GN (1966) Tetanus. State Publishing House “Medicine” Moscow Kryzhanovsky GN (1973) The mechanism of action of tetanus toxin: effect on synaptic processes and some particular features of toxin binding by the nervous tissue. Naunyn Schmiedebergs Arch Pharmacol 276:247–270Google Scholar
  173. Kryzhanovsky GN (1975 a) Present data on the pathogenesis of tetanus. Prog Drug Res 19:301–313PubMedGoogle Scholar
  174. Kryzhanovsky GN (1975b) Tetanus: general and pathophysiological aspects. Achievements, failures, perspectives of elaboration of the problem. Prog Drug Res 19:314–322PubMedGoogle Scholar
  175. Kryzhanovsky GN (1981) Pathophysiology. In: Veronesi R (ed) Tetanus. Important new concepts. Excerpta Medica, Amsterdam, pp 109–182Google Scholar
  176. Kryzhanovsky GN, Rodina VI, Glebov RN, Bazyan AS (1980) Effect of tetanus toxin on noradrenaline liberation from rat brain synaptosomes. Bull Exp Biol Med (Transl) 89:115–118Google Scholar
  177. Laird WJ, Aaronson W, Silver RP, Habig WH, Hardegree MC (1980) Plasmid-associated toxigenicity in Clostridium tetani. J Infect Dis 142:623PubMedGoogle Scholar
  178. Laird WJ, Aaronson W, Habig WH, Hardegree MC, Silver RP (1981) 6th Internatl Conf on Tetanus. Fondation Merieux, Lyon, pp 9–19Google Scholar
  179. Laurence DR, Webster RA (1963) Pathologic physiology, pharmacology and therapeutics of tetanus. Clin Pharmacol Ther 4:36–73Google Scholar
  180. Lazarovici P, Yavin E (1985 a) Tetanus toxin interaction with human erythrocytes. I. Properties of polysialoganglioside association with the cell surface. Biochim Biophys Acta 812:523–531PubMedGoogle Scholar
  181. Lazarovici P, Yavin E (1985b) Tetanus toxin interaction with human erythrocytes. II. Kinetic properties of toxin association and evidence for a ganglioside-toxin macromolecular complex formation. Biochim Biophys Acta 812:532–542PubMedGoogle Scholar
  182. Lazarovici P, Tayot JL, Yavin E (1984) Affinity chromatographic purification and characterization of two iodinated tetanus toxin fractions exhibiting different binding properties. Toxicon 22:401–413PubMedGoogle Scholar
  183. Ledeen R (1985) Gangliosides of the neuron. Trends Neurosci 8:169–174Google Scholar
  184. Ledley FD, Lee G, Kohn LD, Habig WH, Hardegree MC (1977) Tetanus toxin interactions with thyroid plasma membranes. Implications for structure and function of tetanus toxin receptors and potential pathophysiological significance. J Biol Chem 252:4049–4055PubMedGoogle Scholar
  185. Lee PM, Grant CWM (1980) Ganglioside head group disorder as a sequel to lectin binding. Biochem Biophys Res Comm 95:1299–1305PubMedGoogle Scholar
  186. Lee G, Grollmann EF, Dyer S, Beguinod F, Kohn D, Habig WH, Hardegree MC (1979) Tetanus toxin and thyrotropin interactions with rat-brain membrane preparations. J Biol Chem 254:3826–3832PubMedGoogle Scholar
  187. Lewis GE (ed) (1981) Biomedical aspects of botulism. Academic, New YorkGoogle Scholar
  188. Lietzke R, Unsicker K (1983) Tetanus toxin binding to different morphological phenotypes of cultured rat and bovine adrenal medullary cells. Neurosci Lett 38:233–238PubMedGoogle Scholar
  189. Llados F, Matteson DR, Kriebel ME (1980) β-Bungarotoxin preferentially blocks one class of miniature end-plate potentials. Brain Res 192:598–602PubMedGoogle Scholar
  190. Lundh H (1978) Effects of 4-aminopyridine on neuromuscular transmission. Brain Res 153: 307–318PubMedGoogle Scholar
  191. Lundh H (1983) Antagonism of botulinum toxin paralysis by low temperature. Muscle Nerve 6:56–60PubMedGoogle Scholar
  192. Lundh H, Leander S, Thesleff S (1977) Antagonism of the paralysis produced by botulinum toxin in the rat. J Neurol Sci 32:29–43PubMedGoogle Scholar
  193. Macdonald RL, Barker JL (1978) Specific antagonism of GABA-mediated postsynaptic inhibition in cultured spinal cord neurons: a common mode of convulsant action. Neurology (NY) 28:325–330Google Scholar
  194. Major RH (1965) Classic descriptions of disease. Thomas, SpringfieldGoogle Scholar
  195. Marie A (1898) Recherches sur les proprietes antitetaniques des centres nerveux de l’animal sain. Ann Inst Pasteur 12:91–95Google Scholar
  196. Matsuda M, Yoneda M (1974) Dissociation of tetanus neurotoxin into two polypeptide fragments. Biochem Biophys Res Commun 57:1257–1262PubMedGoogle Scholar
  197. Matsuda M, Yoneda M (1975) Isolation and purification of two antigenically active, “complementary” polypeptide fragments of tetanus neurotoxin. Infect Immun 12:1147–1153PubMedGoogle Scholar
  198. Matsuda M, Yoneda M (1976) Reconstitution of tetanus neurotoxin from two antigenically active polypeptide fragments. Biochem Biophys Res Commun 68:668–674PubMedGoogle Scholar
  199. Matsuda M, Yoneda M (1977) Antigenic substructure of tetanus neurotoxin. Biochem Biophys Res Commun 77:268–274PubMedGoogle Scholar
  200. McGeer PL, McGeer EG (1979) Use of the neurotoxic agents kainic acid and tetanus toxin in the extrapyramidal system. Adv Cytopharm 3:437–446Google Scholar
  201. McGeer PL, McGeer EG, Campbell JJ (1980) Rotatory effects of intra-cerebral tetanus toxin injections. Exp Neurol 67:363–367PubMedGoogle Scholar
  202. Meldolesi MF, Fishman PH, Aloj SM, Ledley FD, Lee G, Bradley RM, Brady RO, Kohn LD (1977) Separation of the glycoprotein and ganglioside components of thyrotropin receptor activity in plasma membranes. Biochem Biophys Res Commun 75:581–588PubMedGoogle Scholar
  203. Mellanby J (1984) Comparative activities of tetanus and botulinum toxins. Neuroscience 11:29–34PubMedGoogle Scholar
  204. Mellanby J, Green J (1981) Commentary. How does tetanus toxin act? Neuroscience 6:281–300PubMedGoogle Scholar
  205. Mellanby J, Pope D (1976) The relationship between the action of tetanus toxin and its binding by membranes and gangliosides. In: Porcellati G, Ceccarelli B, Tettamanti G (eds) Ganglioside Function: Biochemical and Pharmacological Implications. Plenum Press, New York, pp 215–229Google Scholar
  206. Mellanby J, Thompson PA (1972) The effect of tetanus toxin at the neuromuscular junction in the goldfish. J Physiol (Lond) 224:407–419Google Scholar
  207. Mellanby J, Thompson PA (1981) The interaction of tetanus toxin and lanthanum at the neuromuscular junction in the goldfish. Toxicon 19:547–554PubMedGoogle Scholar
  208. Mellanby J, Whittaker VP (1968) The fixation of tetanus toxin by synaptic membranes. J Neurochem 15:205–208PubMedGoogle Scholar
  209. Meyer H, Ransom F (1903) Untersuchungen über den Tetanus. Arch Exp Path Pharmakol 49:369–416Google Scholar
  210. Mirsky R, Wendon LMB, Black P, Stolkin C, Bray D (1978) Tetanus toxin: a cell surface marker for neurons in culture. Brain Res 148:251–259PubMedGoogle Scholar
  211. Molgo J, Thesleff S (1982) 4-Aminoquinoline-induced ‘giant’ miniature end-plate potentials at mammalian neuromuscular junctions. Proc R Soc Lond B 214:229–247PubMedGoogle Scholar
  212. Molgo J, Thesleff S (1984) Studies on the mode of action of botulinum toxin type A at the frog neuromuscular junction. Brain Res 297:309–316PubMedGoogle Scholar
  213. Montesano R, Roth J, Robert A, Orci L (1982) Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins. Nature 296:651–653PubMedGoogle Scholar
  214. Morris NP, Consiglio E, Kohn L, Habig D, Hardegree WH, Helting TB (1980) Interaction of fragment-B and fragment-C of tetanus toxin with neural and thyroid membranes and with gangliosides. J Biol Chem 255:6071–6076PubMedGoogle Scholar
  215. Moss J, Fishman PH, Watkins PA (1980) In vitro degradation of 125I-choleragen by normal human fibroblasts. In: Proc 15th Joint Conference on Cholera. US Dept HEW, NIH Publ No 80–2003, pp 279–288Google Scholar
  216. Mullin BR, Fishman RH, Lee G, Aloj SM, Ledley FD, Winand RJ, Kohn LD, Brady RO (1976) Thyrotropin-ganglioside interactions and their relationship to the structure and function of thyrotropin receptors. Proc Natl Acad Sci USA 73:842–846PubMedGoogle Scholar
  217. Murayama S, Syuto B, Oguma K, Iida H, Kubo S (1984) Comparison of Clostridium botulinum toxin types D and C1 in molecular property, antigenicity and binding ability to rat-brain synaptosomes. Eur J Biochem 142:487–492PubMedGoogle Scholar
  218. Nagata I, Keilhauer G, Schachner M (1986) Neuronal influence on antigenic marker profile, cell shape and proliferation of cultured astrocytes obtained by microdissection of distinct layers from the early postnatal mouse cerebellum. Develop Brain Res 24:217–232Google Scholar
  219. Nässl DR (1981) Transneuronal labeling with horseradish peroxidase in the visual system of the house fly. Brain Res 206:431–438Google Scholar
  220. Neubauer V, Helting TB (1979) Structure of tetanus toxin. N-terminal amino acid analysis of the two molecular forms of tetanus toxin and its composite chains. Biochem Biophys Res Commun 86:635–642PubMedGoogle Scholar
  221. Neubauer V, Helting TB (1981) Structure of tetanus toxin. The arrangement of papain digestion products within the heavy chain-light chain framework of extracellular toxin. Biochim Biophys Acta 668:141–148PubMedGoogle Scholar
  222. Neville DM, Chang TM (1978) Receptor-mediated protein transport into cells. Entry mechanisms for toxins, hormones, antibodies, viruses, lysosomal hydrolyses, asialoglycoproteins, and carrier proteins. Curr Top Membrane Transp 10:65–150Google Scholar
  223. Nishida S, Yamagishi T, Tamai K, Sanada I, Takahashi K (1969) Effects of heat selection on toxigenicity, cultural properties and antigenic structures of Clostridia. J Infect Dis 120:507–516PubMedGoogle Scholar
  224. Nisticó G, Mastroeni P, Pitzurra M (eds) (1985) Seventh International Conference on Tetanus, Gangemi Publ., RomeGoogle Scholar
  225. Ohishi I (1983 a) Lethal and vascular permeability activities of botulinum C2 toxin induced by separate injections of the two toxin components. Infect Immun 40:336–339PubMedGoogle Scholar
  226. Ohishi I (1983b) Response of mouse intestinal loop to botulinum C2 toxin: enterotoxic activity induced by cooperation of non-linked protein components. Infect Immun 40:691–695PubMedGoogle Scholar
  227. Ohishi I, Sakaguchi G (1977) Activation of botulinum toxins in the absence of nicking. Infect Immun 17:402–407PubMedGoogle Scholar
  228. Ohishi I, Iwasaki M, Sakaguchi G (1980 a) Purification and characterization of two components of botulinum C2 toxin. Infect Immun 30:668–673PubMedGoogle Scholar
  229. Ohishi I, Iwasaki M, Sakaguchi G (1980b) Vascular permeability activity of botulinum C2 toxin elicited by cooperation of two dissimilar protein components. Infect Immun 31:890–895Google Scholar
  230. Ohishi I, Miyake M, Ogura H, Nakamura S (1984) Cytopathic effect of botulinum C2 toxin on tissue culture cells. FEMS Microbiol Lett 23:281–284Google Scholar
  231. Oilman M, Galla HJ (1985) Ganglioside headgroups decrease lipid order in reconstituted phosphatidylcholine liposomes. FEBS Lett 179:173–176Google Scholar
  232. Osborne RH, Bradford HF (1973) Tetanus toxin inhibits amino acid release from nerve endings in vitro. Nature (New Biol) 244:157–158Google Scholar
  233. Pearce BR, Gard AL, Dutton GR (1983) Tetanus toxin inhibition of K+-stimulated 3H-GABA release from developing cell cultures of rat cerebellum. J Neurochem 40:887–890PubMedGoogle Scholar
  234. Polak RL, Sellin LC, Thesleff S (1981) Acetylcholine content and release in denervated or botulinum-poisoned rat skeletal muscle. J Physiol (Lond) 319:253–259Google Scholar
  235. Prescott LM, Altenbern RA (1967 a) Detection of bacteriophages from two strains of Clostridium tetani. J Virol 1:1085–1086PubMedGoogle Scholar
  236. Prescott LM, Altenbern RA (1967b) Inducible lysis in Clostridium tetani. J Bacteriol 93:1220–1225PubMedGoogle Scholar
  237. Prévot AR (1955) Biologie des maladies dues aux anérobies. Collection de l’Institut Pasteur. Edit. Medical Flammarion, ParisGoogle Scholar
  238. Price DL, Griffin JW (1977) Tetanus toxin: retrograde axonal transport of systemically administered toxin. Neuro sei Lett 4:61–65Google Scholar
  239. Price DL, Griffin JW, Peck K (1977) Tetanus toxin: evidence for binding at synaptic nerve endings. Brain Res 121:379–384PubMedGoogle Scholar
  240. Proia RL, Hart DA, Holmes RK, Holmes KV, Eideis L (1979) Immunoprecipitation and partial characterization of diphtheria toxin-binding glycoproteins from surface of guinea-pig cells. Proc Natl Acad Sci USA 76:685–689PubMedGoogle Scholar
  241. Pumplin DW, del Castillo J (1975) Release of packets of acetylcholine and synaptic vesicles elicited by brown widow spider venom in frog motor nerve endings poisoned by botulinum toxin. Life Sci 17:137–142PubMedGoogle Scholar
  242. Raff MC, Miller RH, Noble MC (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303:390–396PubMedGoogle Scholar
  243. Raju TR, Dahl D (1982) Immunofluorescence staining of cultured neurones: a comparative study using tetanus toxin and neurofilament antisera. Brain Res 248:196–200PubMedGoogle Scholar
  244. Ramos S, Grollmann EF, Lazo PS, Dyer SHA, Habig WH, Hardegree MC, Kaback HR, Kohn LD (1979) Effect of tetanus toxin on the accumulation of the permeant lipophilic cation tetraphenylphosphonium by guinea pig brain synaptosomes. Proc Natl Acad Sci USA 76:4783–4787PubMedGoogle Scholar
  245. Rey M, Diop-Mar I, Robert D (1981) Treatment of tetanus. In: Veronesi R (ed) Tetanus: important new concepts. Excerpta Medica, Amsterdam, pp 207–237Google Scholar
  246. Roa M, Boquet P (1985) Interaction of tetanus toxin with lipid vesicles at low pH. Protection of specific polypeptides against proteolysis. J Biol Chem 260:6827–6835PubMedGoogle Scholar
  247. Robinson JP, Hash JH (1982) A review of the molecular structure of tetanus toxin. Mol Cell Biochem 48:33–45PubMedGoogle Scholar
  248. Rogers TB, Snyder SH (1981) High-affinity binding of tetanus toxin to mammalian brain membranes. J Biol Chem 256:2402–2407PubMedGoogle Scholar
  249. Sakaguchi G (1983) Clostridium botulinum toxins. Pharmacol Ther 19:165–194Google Scholar
  250. Sathyamoorthy V, DasGupta BR (1985 a) Partial amino acid sequences of the heavy and light chains of botulinum neurotoxin type E. Biochem Biophys Res Comm 127:768–772PubMedGoogle Scholar
  251. Sathyamoorthy V, DasGupta BR (1985 b) Separation, purification, partial characterization and comparison of the heavy and light chains of botulinum neurotoxin types A, B and E. J Biol Chem 260:10461–10466PubMedGoogle Scholar
  252. Schmidt JJ, Sathyamoorthy V, DasGupta BR (1984) Partial amino acid sequence of the heavy and light chains of botulinum neurotoxin type A. Biochem Biophys Res Comm 119:900–905PubMedGoogle Scholar
  253. Schmidt JJ, Sathyamoorthy V, DasGupta BR (1985) Partial amino acid sequences of botulinum neurotoxins types B and E. Arch Biochem 238:544–548Google Scholar
  254. Schmitt A, Dreyer F, John C (1981) At least three sequential steps are involved in the tetanus-induced block of neuromuscular transmission. Naunyn Schmiedebergs Arch Pharmacol 317:326–330PubMedGoogle Scholar
  255. Schnitzer J, Schachner M (1981a) Expression of Thy-1, H-2 and NS-4cell surface antigens and tetanus toxin receptors in early postnatal and adult mouse cerebellum. J Neuroimmunol 1:429–456PubMedGoogle Scholar
  256. Schnitzer J, Schachner M (1981b) Developmental expression of cell type-specific markers in mouse cerebellar cortical cells in vitro. J Neuroimmunol 1:471–487PubMedGoogle Scholar
  257. Schnitzer J, Kim U, Schachner M (1984) Some immature tetanus toxin-positive cells share antigenic properties with subclasses of glial cells. An immunofluorescence study in developing nervous system of the mouse using a new monoclonal antibody S1. Devel Brain Res 16:203–217Google Scholar
  258. Schwab ME, Thoenen H (1976) Electron-microscopic evidence for a trans-synaptic migration of tetanus toxin in spinal cord motoneurons: an autoradiographic and morphometric study. Brain Res 105:213–227PubMedGoogle Scholar
  259. Schwab ME, Thoenen H (1977) Retrograde axonal and trans-synaptic transport of macromolecules: physiological and pathophysiological importance. Agents Actions 7:361–368PubMedGoogle Scholar
  260. Schwab ME, Thoenen H (1978) Selective-binding, uptake and retrograde transport of tetanus toxin by nerve terminals in the rat iris. An electron-microscopic study using colloidal gold as a tracer. J Cell Biol 77:1–13PubMedGoogle Scholar
  261. Schwab M, Agid Y, Glowinski J, Thoenen H (1977) Retrograde axonal transport of 125I-tetanus toxin as a tool for tracing fiber connections in the central nervous system. Connections of the rostral part of the rat neostriatum. Brain Res 126:211–224PubMedGoogle Scholar
  262. Schwab ME, Suda K, Thoenen H (1979) Selective retrograde trans-synaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport. J Cell Biol 82:798–810PubMedGoogle Scholar
  263. Schwartz JH (1979) Axonal transport: components, mechanisms, and specificity. Ann Rev Neurosci 2:467–504PubMedGoogle Scholar
  264. Sellin LC, Thesleff S (1981) Pre- and post-synaptic actions of botulinum toxin at the rat neuromuscular junction. J Physiol (Lond) 317:487–495Google Scholar
  265. Sellin LC, Kauffman JA, DasGupta BR (1983 a) Comparison of the effects of botulinum neurotoxin types A and E at the rat neuromuscular junction. Med Biol 61:120–125PubMedGoogle Scholar
  266. Sellin LC, Thesleff S, DasGupta BR (1983 b) Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction. Acta Physiol Scand 119:127–133PubMedGoogle Scholar
  267. Sellin LC, Kauffman JA, Way JF, Siegel LS (1983 c) Comparison of the action of types A and F botulinum toxin at the rat neuromuscular junction. Soc Neurosci Abstr 9Google Scholar
  268. Semba T, Kano M (1969) Glycine in the spinal cord of cats with local tetanus rigidity. Science 164:571–572PubMedGoogle Scholar
  269. Sherrington CS (1905) On reciprocal innervation of antagonistic muscles — eighth note. Proc R Soc Lond (Biol) 76:269–297Google Scholar
  270. Shone CC, Hambleton P, Melling J (1985) Inactivation of Clostridium botulinum type A neurotoxin by trypsin and purification of two tryptic fragments. Proteolytic action near the COOH-terminus of the heavy subunit destroys toxin-binding activity. Eur J Biochem 151:75–82PubMedGoogle Scholar
  271. Simpson LL (1974) Studies on the binding of botulinum toxins type A to the rat phrenic nerve- hemidiaphragm preparation. Neuropharmacol 13:683–691Google Scholar
  272. Simpson LL (1978) Pharmacological studies on the subcellular site of action of botulinum toxin type A. J Pharmacol Exp Ther 206:661–669PubMedGoogle Scholar
  273. Simpson LL (1980) Kinetic studies on the interaction between botulinum toxin type A and the cholinergic neuromuscular junction. J Pharmacol Exp Ther 212:16–21PubMedGoogle Scholar
  274. Simpson LL (1981) The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev 33:155–188PubMedGoogle Scholar
  275. Simpson LL (1982) A comparison of the pharmacological properties of Clostridium botulinum Cl and C2 toxins. J Pharmacol Exp Ther 223:695–701PubMedGoogle Scholar
  276. Simpson LL (1984 a) Fragment C of tetanus toxin antagonizes the neuromuscular blocking properties of native tetanus toxin. J Pharmacol Exp Ther 228:600–605PubMedGoogle Scholar
  277. Simpson LL (1984 b) Botulinum toxin and tetanus toxin recognize similar membrane determinants. Brain Res 305:177–180PubMedGoogle Scholar
  278. Simpson LL (1984c) The binding fragment from tetanus toxin antagonizes the neuromuscular blocking actions of botulinum toxin. J Pharmacol Exp Ther 229:182–187PubMedGoogle Scholar
  279. Simpson LL (1984d) Molecular basis for the pharmacological actions of Clostridium botulinum type C2 toxin. J Pharmacol Exp Ther 230:665–669PubMedGoogle Scholar
  280. Simpson LL (1985) Pharmacological experiments on the binding and internalization of the 50000-dalton carboxy terminus of tetanus toxin at the cholinergic neuromuscular junction. J Pharmacol Exp Ther 234:100–105PubMedGoogle Scholar
  281. Simpson LL, Hoch DH (1985) Neuropharmacological characterization of fragment B from tetanus toxin. J Pharmacol Exp Ther 232:223–227PubMedGoogle Scholar
  282. Simpson LL, Rapport MM (1971) Ganglioside inactivation of botulinum toxin. J Neurochem 18:1341–1343PubMedGoogle Scholar
  283. Smith LA, Middlebrook JL (1985) Botulinum and tetanus neurotoxins inhibit guanylate cyclase activity in synaptosomes and cultured nerve cells. Toxicon 23:611Google Scholar
  284. Smith LD (1977) Botulism. The organism, its toxins, the disease. Thomas, SpringfieldGoogle Scholar
  285. Spitzer N (1972) Miniature end-plate potentials at mammalian neuromuscular junctions poisoned by botulinum toxin. Nature 237:26–27Google Scholar
  286. Stanley EF, Drachman DB (1983) Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction. Brain Res 261:172–175PubMedGoogle Scholar
  287. Stöckel K, Schwab M, Thoenen H (1975) Comparison between the retrograde axonal transport of nerve growth factor and tetanus toxin in motor, sensory and adrenergic neurons. Brain Res 99:1–16PubMedGoogle Scholar
  288. Stöckel K, Schwab M, Thoenen H (1977) Role of gangliosides in the uptake and retrograde axonal transport of cholera and tetanus toxin as compared to nerve growth factor and wheat germ agglutinin. Brain Res 132:273–285Google Scholar
  289. Sugimoto N, Higashida H, Ozutsumi K, Miki N, Matsuda M (1983) Tetanus toxin blocks Ca spikes in neuroblastoma clone NIE-115 cells. Biochem Biophys Res Comm 115:788–793PubMedGoogle Scholar
  290. Sugiyama H (1980) Clostridium botulinum neurotoxin. Microbiol Rev 44:419–448PubMedGoogle Scholar
  291. Syuto B, Kubo S (1981) Separation and characterization of heavy and light chains from Clostridium botulinum type C toxin and their reconstitution. J Biol Chem 256:3712–3718PubMedGoogle Scholar
  292. Tarlov IM, Ling H, Yamada H (1973) Neuronal pathology in experimental local tetanus: clinical implications. Neurology 23:580–591PubMedGoogle Scholar
  293. Taylor CF, Britton P, van Heyningen S (1983) Similarities in the heavy and light chains of tetanus toxin suggested by their amino acid compositions. Biochem J 209:897–899PubMedGoogle Scholar
  294. Thesleff S (1960) Supersensitivity of skeletal muscle produced by botulinum toxin. J Physiol (Lond) 151:598–607Google Scholar
  295. Thesleff S, Molgo J, Lundh H (1983) Botulinum toxin and 4-aminoquinoline induce a similar abnormal type of spontaneous quantal transmitter release at the rat neuromuscular junction. Brain Res 264:89–97PubMedGoogle Scholar
  296. Tomono Y, Naito I, Watanabe K (1984) Glycosphingolipid pattern of rat kidney. Dependence of age and sex. Biochim Biophys Acta 796:199–204PubMedGoogle Scholar
  297. Tonge DA (1974) Chronic effects of botulinum toxin on neuromuscular transmission and sensitivity to acetylcholine in slow and fast skeletal muscle of the mouse. J Physiol (Lond) 241:127–139Google Scholar
  298. Tremblay JP, Laurie RE, Colonnier M (1983) Is the MEPP due to the release of one vesicle or to the simultaneous release of several vesicles at one active zone? Brain Res Rev 6:299–314Google Scholar
  299. Trojanowski J, Schmidt ML (1984) Interneuronal transfer of axonally transported proteins: studies with HRP and HRP conjugates of wheat germ agglutinin, cholera toxin and the B subunit of cholera toxin. Brain Res 311:366–369PubMedGoogle Scholar
  300. Trojanowski J, Gonatas JO, Gonatas NK (1981) Conjugates of horseradish peroxidase (HRP) with cholera toxin and wheat germ agglutinin are superior to free HRP as orthogradely transported markers. Brain Res 223:381–385PubMedGoogle Scholar
  301. Turpin A, Raynaud M (1959) La toxine tetanique. Ann Inst Pasteur 97:718–732Google Scholar
  302. van Heyningen S (1976) Binding of ganglioside by the chains of tetanus toxin. FEBS Lett 68:5–7PubMedGoogle Scholar
  303. van Heyningen S (1980) Tetanus toxin. Pharmacol Ther 11:141–157PubMedGoogle Scholar
  304. van Heyningen S (1984) The action of cholera toxin. In: Alouf JE, Fehrenbach FJ, Freer JH, Jeljaszewicz J (eds) Bacterial protein toxins. Academic London, pp 347–352Google Scholar
  305. van Heyningen WE (1974) Les recepteurs des membranes cellulaires pour les toxines tetaniques et choleriques ou les delices de l’ignorance. Bull Inst Pasteur 72:433–464Google Scholar
  306. van Heyningen WE, Mellanby J (1968) The effects of cerebrosides and other lipids on the fixation of tetanus toxin by ganglioside. J Gen Microbiol 52:447–454Google Scholar
  307. van Heyningen WE, Mellanby JH (1971) Tetanus toxin. In: Kadis S, Montie TC, Ajl SJ (eds) Microbial toxins. II. Academic, New York, London, pp 69–108Google Scholar
  308. van Heyningen WE, Mellanby J (1973) A note on the specific fixation, specific deactivation and nonspecific inactivation of bacterial toxins by gangliosides. Naunyn Schmiedebergs Arch Pharmacol 276:297–302PubMedGoogle Scholar
  309. Veronesi R (ed) (1981) Tetanus. Important new concepts. Excerpta Medica, Amsterdam, Oxford, PrincetonGoogle Scholar
  310. Vinét G, Frédette V (1968) Un bacteriophage dans une culture de Clostridium botulinum C. Rev Can Biol Exp 27:73–74Google Scholar
  311. Vuillamy T, Messenger EA (1981) Tetanus toxin: a marker of amphibian neuronal differentiation in vitro. Neurosci Lett 22:87–90Google Scholar
  312. Vyskocil F, Illes P (1977) Non-quantal release of transmitter at mouse neuromuscular junction and its dependence on the activity of Na+-K+ATPase. Pflügers Arch 370:295–297PubMedGoogle Scholar
  313. Ward WHJ, Britton P, van Heyningen S (1981) The hydrophobicities of cholera toxin, tetanus toxin and their components. Biochem J 199:457–460PubMedGoogle Scholar
  314. Wassermann A, Takaki I (1898) Über tetanusantitoxische Eigenschaften des normalen Centralnerven-systems. Klin Wochenschr 35:5–6Google Scholar
  315. Weiler U, Taylor C, Habermann E (1986) Quantitative comparison between tetanus toxin, some fragments and toxoid for binding and axonal transport in the rat. Toxicon (in press)Google Scholar
  316. Wellhöner HH (1982) Tetanus neurotoxin. Rev Physiol Biochem Pharmacol 93:1–68PubMedGoogle Scholar
  317. Wendon LMB (1980) On the action of tetanus toxin at the rat neuromuscular junction. J Physiol (Lond) 300:23 PGoogle Scholar
  318. Wendon LMB, Gill DM (1982) Tetanus toxin action on cultured nerve cells. Does it modify a neuronal protein? Brain Res 238:292–297PubMedGoogle Scholar
  319. Wenthold RJ, Skaggs KK, Reale RR (1984) Retrograde axonal transport of antibodies to synaptic membrane components. Brain Res 304:162–165PubMedGoogle Scholar
  320. Wernig A, Stöver H, Tonge D (1977) The labelling of motor end-plates in skeletal muscle of mice with 125I tetanus toxin. Naunyn Schmiedebergs Arch Pharmacol 298:37–42PubMedGoogle Scholar
  321. Wiegand H, Wellhöner HH (1977) The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex. Naunyn Schmiedebergs Arch Pharmacol 298:235–238PubMedGoogle Scholar
  322. Wiegand H, Erdmann G, Wellhöner HH (1976) 125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. Naunyn Schmiedebergs Arch Pharmacol 292:161–165PubMedGoogle Scholar
  323. Wieraszko A (1985) Attenuation of inhibitory processes in the central nervous system by tetanus toxin: An in vitro study on rat hippocampal slices. Life Sci 37:2059–2065PubMedGoogle Scholar
  324. Williams RS, Tse CK, Dolly JO, Hambleton P, Melling J (1983) Radio-iodination of botulinum neurotoxin type A with retention of its biological activity and its binding to brain synaptosomes. Eur J Biochem 131:437–445PubMedGoogle Scholar
  325. Wonnacott S, Marchbanks RM (1976) Inhibition by botulinum toxin of depolarization-evoked release of 14C acetylcholine release from synaptosomes in vitro. Biochem J 156:701–712PubMedGoogle Scholar
  326. Wright GP (1955) The neurotoxins of Clostridium botulinum and Clostridium tetani. Pharmacol Rev 7:413–465PubMedGoogle Scholar
  327. Yamaizumi M, Uchida T, Takamatsu K, Okada Y (1982) Intracellular stability of diphtheria toxin fragment A in the presence and absence of anti-fragment A antibody. Proc Natl Acad Sci USA 79:461–465PubMedGoogle Scholar
  328. Yavin E, Habig WH (1984) Binding of tetanus toxin to somatic neural hybrid cells with varying ganglioside composition. J Neurochem 42:1313–1320PubMedGoogle Scholar
  329. Yavin E, Yavin Z, Habig WH, Hardegree MC, Kohn LD (1981) Tetanus toxin association with developing neuronal cell cultures. Kinetic parameters and evidence for ganglioside-mediated internalization. J Biol Chem 256:7014–7022PubMedGoogle Scholar
  330. Yavin E, Yavin Z, Kohn LD (1983) Temperature-mediated interaction of tetanus toxin with cerebral neuron cultures: characterization of a neuraminidase-insensitive toxin receptor complex. J Neurochem 40:1212–1219PubMedGoogle Scholar
  331. Yavin E (1984) Gangliosides mediate association of tetanus toxin with neural cells in culture. Arch Biochem Biophys 230:129–137PubMedGoogle Scholar
  332. Yavin Z, Yavin E, Kohn LD (1982) Sequestration of tetanus toxin in developing neuronal cell cultures. J Neurosci Res 7:267–278PubMedGoogle Scholar
  333. Zalman LS, Wisnieski BJ (1984) Mechanism of insertion of diphtheria toxin: peptide entry and pore size determinations. Proc Natl Acad Sci USA [Biol Sci] 81:3341–3346Google Scholar
  334. Zimmermann JM, Piffaretti JCI (1977) Interaction of tetanus toxin and toxoid with cultured neuroblastoma cells. Analysis by immunofluorescence. Naunyn Schmiedebergs Arch Pharmacol 296:271–277Google Scholar
  335. Zimmermann W, Dreyer F, Schmitt A (1981) Immunohistochemical localization of tetanus toxin binding at the motor end-plates of frog and mouse. Pflügers Arch 391: R 40Google Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1986

Authors and Affiliations

  • E. Habermann
    • 1
  • F. Dreyer
    • 1
  1. 1.Rudolf-Buchheim-Institut für Pharmakologie der Justus-Liebig-Universität GießenGießenGermany

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