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Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of β-bungarotoxin, crotoxin and taipoxin

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Summary

  1. 1.

    β-Bungarotoxin, crotoxin and taipoxin, presynaptic neurotoxins of snake venom origin, have about the same phospholipid-splitting activities as a much less toxic cobra phospholipase A2 in the presence of Ca2+ and deoxycholate.

  2. 2.

    Sr2+ was a much less effective activator of the enzymes than is Ca2+, the activation by Sr2+ being only 3–6% for β-bungarotoxin and crotoxin and 12% for taipoxin.

  3. 3.

    Sr2+ also inhibited the Ca2+-activated enzymes by 80% in the cases of β-bungarotoxin and crotoxin, but only 16% in the case of taipoxin.

  4. 4.

    Mg2+ had no significant effect on β-bungarotoxin or crotoxin, but activated taipoxin in the presence or absence of Ca2+.

  5. 5.

    In Sr2+-Tyrode lacking Ca2+ all three toxins exhibited the same immediate depression followed by facilitation in the rat and mouse diaphragms, but the final blocking activity was only 3–10% with β-bungarotoxin and crotoxin and was 30% with taipoxin.

  6. 6.

    In Sr2+-Tyrode, increasing in the rate of nerve stimulation had less accelerating effect on the development of neuromuscular block than in Ca2+-Tyrode for any of the toxins.

  7. 7.

    Removal of Mg2+ from Sr2+-Tyrode did not diminish the potency of taipoxin in blocking neuromuscular transmission, suggesting that enzyme activity at the outer surface of the axolemma does not contribute to the neuromuscular blocking action.

  8. 8.

    All of the results indicate that there are close correlations between the presynaptic activities of these toxins and their phospholipid-splitting activities in the cationic environment prevailing in the axoplasm. Apparently the final blocking effect of these toxins is due to phospholipase A action within the nerve terminal.

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Authors and Affiliations

  1. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    C. Chiung Chang, M. Jai Su & J. Don Lee

  2. Institute of Biochemistry, Biomedical Center, University of Uppsala, Box 574, S-751 23, Uppsala

    David Eaker

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  1. C. Chiung Chang
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  2. M. Jai Su
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  3. J. Don Lee
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  4. David Eaker
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Chang, C.C., Su, M.J., Lee, J.D. et al. Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of β-bungarotoxin, crotoxin and taipoxin. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 155–161 (1977). https://doi.org/10.1007/BF00498557

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