Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 296, Issue 2, pp 159–168 | Cite as

Crotoxin, the neurotoxin of South American rattlesnake venom, is a presynaptic toxin acting like β-bungarotoxin

  • C. Chiung Chang
  • J. Dong Lee


  1. 1.

    Crotoxin isolated from the venom of the Brazilian rattlesnake (Crotalus durissus terrificus) by chromatography on CM-Sephadex and Sephadex G-75 caused respiratory paralysis accompanied by peripheral neuromuscular blockade.

  2. 2.

    The chicken was more sensitive to crotoxin than the mouse whereas the rat was more resistant.

  3. 3.

    There was a slight initial facilitation and latent period before the decline of neuromuscular transmission started. In the media with low Ca2+ or high Mg2+, there was also an immediate depression before the facilitation.

  4. 4.

    The membrane potential, action potential and the response to high K+ of the isolated muscles were not significantly affected.

  5. 5.

    The response to exogenous acetylcholine and the amplitudes of m.e.p.p.s were also not affected.

  6. 6.

    The quantal contents of e.p.p.s were markedly depressed and the amplitudes of successive e.p.p.s elicited by a train of pulses at 100 Hz were well maintained.

  7. 7.

    The frequency of m.e.p.p.s in the mouse diaphragm, but not in the rat muscle, was first increased followed by a decrease when the evoked release of transmitter failed.

  8. 8.

    In the blocked muscle, high K+ was still able to evoke a burst of m.e.p.p.s, though less marked than in the untreated control.

  9. 9.

    The neuromuscular blocking activity of crotoxin was attenuated by an increase of Mg2+, Ca2+ or decrease of Ca2+ but augmented by increasing rates of stimulation.

  10. 10.

    The effect of crotoxin continued to progress even after washout.

  11. 11.

    The effects of crotoxin are very similar to those of β-bungarotoxin and most likely due to the presynaptic inhibition of the mechanism mediating the release of neurotransmitter in the nerve terminal.


Key words

Crotoxin Neurotoxin β-Bungarotoxin Neuromuscular block Presynaptic action Snake venom 


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  1. Breithaupt, H.: Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 271–278 (1976)Google Scholar
  2. Breithaupt, H., Omori-Satoh, T., Lang, J.: Isolation and characterization of three phospholipase A from the crotoxin complex. Biochim. biophys. Acta (Amst.) 403, 355–369 (1975)Google Scholar
  3. Breithaupt, H., Rübsamen, K., Habermann, E.: In vitro and in vivo interactions between phospholipase A and a novel potentiator isolated from so-called crotoxin. Naunyn-Schmiedebergs Arch. Pharmak. 269, 403–404 (1971)Google Scholar
  4. Bülbring, E.: Observations on the isolated phrenic nerve diaphragm preparation of the rat. Brit. J. Pharmacol. 1, 38–61 (1946)Google Scholar
  5. Castillo, J. del, Katz, B.: Quantal components of the endplate potential. J. Physiol. (Lond.) 124, 560–573 (1954)Google Scholar
  6. Chang, C. C.: The actions of snake venoms on nerve and muscle. In: Snake venoms (C. Y. Lee, ed.). Berlin-Heidelberg-New York: Springer (in press, 1977)Google Scholar
  7. Chang, C. C., Chen, T. F., Lee, C. Y.: Studies of the presynaptic effect of β-bungarotoxin on neuromuscular transmission. J. Pharmacol. exp. Ther. 184, 339–345 (1973)Google Scholar
  8. Chang, C. C., Huang, M. C.: Comparison of the presynaptic actions of botulinum toxin and β-bungarotoxin on neuromuscular transmission. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 129–142 (1974)Google Scholar
  9. Chang, C. C., Lee, C. Y.: Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuro-muscular blocking action. Arch. intern. Pharmacodyn. 144, 241–257 (1963)Google Scholar
  10. Chang, C. C., Lee, C. Y.: Electrophysiological study of neuromuscular blocking action of cobra neurotoxin. Brit. J. Pharmacol. 28, 172–181 (1966)Google Scholar
  11. Chen, I.-L., Lee, C. Y.: Ultrastructural changes in the motor nerve terminals caused by β-bungarotoxin. Virchows Arch., Abt. B, Zellpath. 6, 318–325 (1970)Google Scholar
  12. Cheymol, J., Gonçalves, J. M., Bourillet, F., Roch-Arveiler, M.: Action neuromusculaire comparée de la crotamine et du venin de Crotalus durissus terrificus var. Crotaminicus I. Sur preparations neuromusculaires in situ. Toxicon 9, 279–286 (1971a)Google Scholar
  13. Cheymol, J., Gonçalves, J. M., Bourillet, F., Roch-Arveiller, M.: Action neuromusculaire comparée de la crotamine et du venin du Crotalus durissus terrificus var. Crotaminicus II. Sur preparations isolées. Toxicon 9, 287–289 (1971b)Google Scholar
  14. Cull-Candy, S. G., Fohlman, J., Gustavsson, D., Lüllmann-Rauch, R., Thesleff, S.: The effect of taipoxin and notexin on the function and fine structure of the murine neuromuscular junction. J. Neurosci. 1, 175–180 (1976)Google Scholar
  15. Eaker, D.: Snake venom toxins reacting post-and presynaptically at the neuromuscular junction. Bull. Inst. Pasteur 74, 7–9 (1976)Google Scholar
  16. Ginsborg, B. L., Warriner, J.: The isolated chick biventer cervicis nerve-muscle preparation. Brit. J. Pharmacol. 15, 410–411 (1960)Google Scholar
  17. Harris, J. B., Karlsson, E., Thesleff, S.: Effects of an isolated toxin from Australian tiger snake (Notechis scutatus scutaus) venom at the mammalian neuromuscular junction. Brit. J. Pharmacol. 47, 141–146 (1973)Google Scholar
  18. Hendon, R. A., Fraenkel-Conrat, H.: Biological roles of the two components of crotoxin. Proc. nat. Acad. Sci. (Wash.) 68, 1560–1563 (1971)Google Scholar
  19. Kamenskaya, M. A., Thesleff, S.: Neuromuscular blocking action of an isolated toxin from the elapid (Oxyuranus scutellatus). Acta physiol. scand. 90, 716–724 (1974)Google Scholar
  20. Lee, C. Y.: Chemistry and pharmacology of purified toxins from Elapid and Sea snake venoms. 5th Int. Congr. Pharmacol., San Francisco 1972, vol. 2, 210–232 (1973)Google Scholar
  21. Lee, C. Y., Chang, S. L., Kau, S. T., Lu, S. H.: Chromatographic separation of the venom of Bungarus multicinctus and characterization of its components. J. Chromatogr. 72, 71–82 (1972)Google Scholar
  22. Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949)Google Scholar
  23. Rübsamen, K., Breithaupt, H., Habermann, E.: Biochemistry and pharmacology of the crotoxin complex. I. Subfractionation and recombination of the crotoxin complex. Naunyn-Schmiedebergs Arch. Pharmak. 270, 274–288 (1971)Google Scholar
  24. Slotta, K., Fraenkel-Conrat, H.: Schlangengifte. III. Reinigung und Krystallisation von Klapperschlangengift. Ber. dtsch. chem. Ges. 71, 1076–1081 (1938)Google Scholar
  25. Strong, P. N., Goerke, J., Oberg, S. G., Kelly, R. B.: β-Bungarotoxin, a presynaptic toxin with enzymatic activity. Proc. nat. Acad. Sci. (Wash.) 73, 178–182 (1976)Google Scholar
  26. Strydom, D. J.: Snake venom toxins. Structure-function relationships and phylogenetics. Comp. Biochem. Physiol. 44B, 269–281 (1973)Google Scholar
  27. Tsai, M. C.: Studies on the ultrastructural changes in the motor nerve terminals caused by β-bungarotoxin. Ph.D. Dissertation. National Taiwan University, Taipei, Taiwan (1975)Google Scholar
  28. Vital Brazil, O.: Pharmacology of crystalline crotoxin. II. Neuromuscular blocking action. Mem. Inst. Butantan 33, 981–992 (1966)Google Scholar
  29. Vital Brazil, O.: Venoms. Their inhibitory action on neuromuscular transmittance. Int. Encycl. Pharmacol. Ther. 14, 145–167 (1972)Google Scholar
  30. Vital Brazil, O., Excell, B. J.: Action of crotoxin and crotactin from the venom of Crotalus durissus terrificus (South American rattlesnake) on the frog neuromuscular junction. J. Physiol. (Lond.) 212, 34p-35p (1971)Google Scholar
  31. Vital Brazil, O., Franceschi, J. P., Waisbich, E.: Pharmacology of crystalline crotoxin. I. Toxicity. Mem. Inst. Butantan 33, 973–980 (1966)Google Scholar
  32. Wernicke, J. F., Vanker, A. D., Howard, B. D.: The mechanism of action of β-bungarotoxin. J. Neurochem. 25, 483–496 (1975)Google Scholar
  33. Yang, C. C.: Chemistry and evolution of toxins in snake venoms. Toxicon 12, 1–43 (1974)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • C. Chiung Chang
    • 1
  • J. Dong Lee
    • 1
  1. 1.Pharmacological Institute, College of MedicineNational Taiwan UniversityTaipeiTaiwan, Republic of China

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