Skip to main content
Log in

Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    The acidic peptide crotapotin potentiated the toxicity of the basic crotalus phospholipase A in all species tested. The order of sensitivity to the lethal action of the phospholipase was: chick > mouse ≧ rabbit > rat. After a latency period of at least 20 min the animals died of respiratory paralysis. Rabbits survived for more than 10 h, if they were artificially respired. The animals recovered very slowly from respiratory depression.

  2. 2.

    In rabbits even high doses of the basic crotalus phospholipase A or its complex with crotapotin1 did not affect the respiratory center nor its reactivity to asphyxia. Conduction of action potentials in the phrenic nerve was not changed.

  3. 3.

    Phospholipase-crotapotin complexes decreased the contractile response of isolated phrenic-hemidiaphragms of rats to direct and indirect stimulation in an irreversible manner. A latency period of 20–100 min preceded the paralysis.

  4. 4.

    A similar block of neuromuscular transmission developed in vivo. After i. v. injection of PC-complexes the contractile response of isolated rat phrenic diaphragms to nerve stimulation was considerably lower than to direct stimulation.

  5. 5.

    Crotalus phospholipase A alone as well as its complex with crotapotin reduced the contractions of the isolated chick biventer cervicis muscle but did not cause a contracture, thus indicating that the phospholipase and PC-complexes act not as depolarizing blockers.

  6. 6.

    Blood pressure, heart rate and electrocardiogram were not substantially altered, when phospholipase A or PC-complex were injected slowly i.v. into rabbits or rats. No cardiotoxic effect was observed in the Langendorff preparation of rat hearts perfused with phospholipase A alone (6×10−6 M) or together with crotapotin (10−5 M). Rapid i.v. injection of the venom produced hypotension. The degree of haemolysis correlated with the enzymatic activity, and was low for the highly toxic PC-complexes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Astrup, P.: Erkennung der Störungen des Säure-Base-Stoffwechsels und ihre klinische Bedeutung. Klin. Wschr. 35, 749–753 (1957)

    Google Scholar 

  • Brazil, O. V.: Pharmacology of crystalline crotoxin. II. Neuromuscular blocking action. Mem. Inst. Butantan, Simp. Internac. 33, 981–992 (1966)

    Google Scholar 

  • Brazil, O. V., 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, 34–35P (1971)

    Google Scholar 

  • Brazil, O. V., Excell, B. J., Sanatana de Sa, S.: The importance of phospholipase A in the action of the crotoxin complex at the frog neuromuscular junction. J. Physiol. (Lond.) 234, 63–64P (1973)

    Google Scholar 

  • Brazil, O. V., Franceschi, J. P., Waisbich, E.: Pharmacology of crystalline crotoxin. I. Toxicity. Mem. Inst. Butantan, Simp. Internac. 33, 973–980 (1966)

    Google Scholar 

  • Breithaupt, H., Habermann, E.: Biochemistry and pharmacology of phospholipase A from Crotalus terrificus venom as influenced by crotapotin. In: Animal and plant toxins, E. Kaiser (ed.), pp. 83–88. München, Goldmann 1973

    Google Scholar 

  • Bülbring, E.: Observations on the isolated phrenic nerve diaphragm preparation of the rat. Brit. J. Pharmacol. 1, 38–61 (1946)

    Google Scholar 

  • Burgen, A. S. V., Dickens, F., Zatman, L. J.: The action of botulinum toxin on the neuro-muscular junction. J. Physiol. (Lond.) 109, 10–24 (1949)

    Google Scholar 

  • 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 

  • Chang, C. C., Chuang, S.-T., Lee, C. Y., Wei, J. W.: Role of cardiotoxin and phospholipase A in the blockade of nerve conduction and depolarization of skeletal muscle induced by cobra venom. Brit. J. Pharmacol. 44, 752–764 (1972)

    Google Scholar 

  • Chang, C. C., Lee, C. Y.: Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuromuscular blocking action. Arch. int. Pharmacodyn. 144, 241–257 (1963)

    Google Scholar 

  • Eaker, D.: Structural nature of pre-synaptic neurotoxins from Australian elapid venoms. Toxicon 13, 90–91 (1975)

    Google Scholar 

  • Ecklebe, G.: Die moderne Cyanhämiglobinbestimmung. Dtsch. med. Wschr. 84, 1531–1532 (1959)

    Google Scholar 

  • Ginsborg, B. L., Warriner, J.: The isolated chick biventer cervicis nerve-muscle preparation. J. Pharmacol. 15, 410–411 (1960)

    Google Scholar 

  • Habermann, E.: Berträge zur Pharmakologie von Phospholipase A. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 230, 538–546 (1957)

    Google Scholar 

  • Habermann, E., Cheng-Raude, D.: Central neurotoxicity of apamin, crotamine, phospholipases A and α-amanitin. Toxicon 13, 465–473 (1975)

    Google Scholar 

  • Harris, J. B., Karlsson, E., Thesleff, S.: Effects of an isolated toxin from Australian Tiger snake (Notechis scutatus scutatus) venom at the mammalian neuromuscular junction. Brit. J. Pharmacol. 47, 141–146 (1973)

    Google Scholar 

  • Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949)

    Google Scholar 

  • Longenecker, H. E., Hurlbut, W. P., Mauro, A., Clark, A. W.: Effects of black widow spider venom on the frog neuromuscular junction. Nature (Lond.) 225, 701–703 (1970)

    Google Scholar 

  • 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 

  • Russell, F. E.: Comparative pharmacology of some animal toxins. Fed. Proc. 26, 1206–1224 (1967)

    Google Scholar 

  • Slotta, K. H., Fraenkel-Conrat, H. L.: Schlangengifte. III. Mitteilung: Reinigung und Krystallisation des Klapperschlangen-Giftes. Ber. dtsch. chem. Ges. 71, 1076–1081 (1938)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Breithaupt, H. Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 271–278 (1976). https://doi.org/10.1007/BF00517389

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00517389

Key words

Navigation