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The presynaptic neuromuscular blocking effect and phospholipase A2 activity of textilotoxin, a potent toxin isolated from the venom of the Australian brown snake, Pseudonaja textilis

Su, M.J.; Coulter, A.R.; Sutherland, S.K.; Chang, C.C.

Toxicon Official Journal of the International Society on Toxinology 21(1): 143-151

1983

ISSN/ISBN: 0041-0101
PMID: 6302954
DOI: 10.1016/0041-0101(83)90057-0
Accession: 044714454
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In the presence of Ca2+ and deoxycholate, textilotoxin has, on a molar basis, about the same phospholipid-splitting activity as β-bungarotoxin and other presynaptically acting toxins. Sr2+ inhibited the enzyme activity in the presence of Ca2+ by about 90%. Textilotoxin blocked neuromuscular transmission without significant change of muscle contractility. As with taipoxin, the mouse diaphragm was more susceptible than the chick biventer cervicis and the rat diaphragm preparations. After complete neuromuscular blockade, the amplitude of spontaneous miniature endplate potentials (m. e. p. p.) and the membrane potential of the mouse diaphragm remained unchanged, as did the contractile response of the chick biventer cervicis muscle to bath-applied acetylcholine. Textilotoxin caused an immediate facilitation of transmitter release in the mouse diaphragm lasting for about 4 min, followed by depression lasting for about 15 min and then a second phase of facilitation lasting for about 25 min, before causing final inhibition. The frequency of m. e. p. p. s was first depressed, then increased twice before the final depression. The time-course, however, was slower than the change of evoked transmitter release. Like all other presynaptic phospholipase A neurotoxins, textilotoxin bound rapidly to the nerve terminal and its blocking effect was antagonized by high Mg2+ and Ca2+ media, but was markedly enhanced on increasing the stimulus frequency from 0.1 Hz to 1.0 Hz. Sr2+ strongly antagonized the neuromuscular blocking effect of textilotoxin only at 1.0 Hz stimulation, but not at 0.1 Hz. It is concluded that textilotoxin acts mainly on the presynaptic nerve terminal, with multiphasic changes of transmitter release. The final blockade is due to its phospholipase A activity acting inside the terminal axolemma.

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Related References

Pearson, J.A.; Tyler, M.I.; Retson, K.V.; Howden, M.E. 1993: Studies on the subunit structure of textilotoxin, a potent presynaptic neurotoxin from the venom of the Australian common brown snake (Pseudonaja textilis). 3. the complete amino-acid sequences of all the subunits Biochimica et Biophysica Acta 1161(2-3): 223-229
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