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. 1976 Aug;73(8):2664–2668. doi: 10.1073/pnas.73.8.2664

Mechanism of action of beta-bungarotoxin on synaptosomal preparations.

I Sen, P A Grantham, J R Cooper
PMCID: PMC430708  PMID: 1066677

Abstract

The neurochemical activity of beta-bungarotoxin was investigated using a synaptosomal preparation of rat cerebral cortices. In preparations preincubated with [3H]choline in order to label acetylcholine the toxin caused a rapid release of the transmitter, which was calcium dependent but only a little affected by a depolarizing concentration of potassium. beta-Bungarotoxin was also shown to be a potent inhibitor of the high affinity transport system for choline, producing 50% inhibition at a concentration of 50 nM. These findings explain the observed electrophysiological effects of the toxin. Electron microscopy revealed no discernible effect of 0.1 muM beta-bungarotoxin on either synaptic vesicles or mitochondria. Neither the release of transmitter nor the inhibition of choline uptake by the toxin was affected by the presence of an inhibitor of phospholipase activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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 Ther. 1963 Jul 1;144:241–257. [PubMed] [Google Scholar]
  2. Chang C. C., Chen T. F., Lee C. Y. Studies of the presynaptic effect of -bungarotoxin on neuromuscular transmission. J Pharmacol Exp Ther. 1973 Feb;184(2):339–345. [PubMed] [Google Scholar]
  3. Clark A. W., Hurlbut W. P., Mauro A. Changes in the fine structure of the neuromuscular junction of the frog caused by black widow spider venom. J Cell Biol. 1972 Jan;52(1):1–14. doi: 10.1083/jcb.52.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collier B., Katz H. S. The synthesis, turnover and release of surplus acetylcholine in a sympathetic ganglion. J Physiol. 1971 May;214(3):537–552. doi: 10.1113/jphysiol.1971.sp009447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cotman C. W. Isolation of synaptosomal and synaptic plasma membrane fractions. Methods Enzymol. 1974;31:445–452. doi: 10.1016/0076-6879(74)31050-6. [DOI] [PubMed] [Google Scholar]
  6. ELLMAN G. L., COURTNEY K. D., ANDRES V., Jr, FEATHER-STONE R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961 Jul;7:88–95. doi: 10.1016/0006-2952(61)90145-9. [DOI] [PubMed] [Google Scholar]
  7. Haga T., Noda H. Choline uptake systems of rat brain synaptosomes. Biochim Biophys Acta. 1973 Jan 26;291(2):564–575. doi: 10.1016/0005-2736(73)90508-7. [DOI] [PubMed] [Google Scholar]
  8. Kelly R. B., Brown F. R., 3rd Biochemical and physiological properties of a purified snake venom neurotoxin which acts presynaptically. J Neurobiol. 1974;5(2):135–150. doi: 10.1002/neu.480050205. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Lee C. Y., Chang C. C. Modes of actions of purified toxins from elapid venoms on neuromuscular transmission. Mem Inst Butantan. 1966;33(2):555–572. [PubMed] [Google Scholar]
  11. Lee C. Y., Chang S. L., Kau S. T., Luh S. H. Chromatographic separation of the venom of Bungarus multicinctus and characterization of its components. J Chromatogr. 1972 Oct 5;72(1):71–82. doi: 10.1016/0021-9673(72)80009-8. [DOI] [PubMed] [Google Scholar]
  12. Lee C. Y. Chemistry and pharmacology of polypeptide toxins in snake venoms. Annu Rev Pharmacol. 1972;12:265–286. doi: 10.1146/annurev.pa.12.040172.001405. [DOI] [PubMed] [Google Scholar]
  13. Lee C. Y. Elapid neurotoxins and their mode of action. Clin Toxicol. 1970 Sep;3(3):457–472. doi: 10.3109/15563657008990119. [DOI] [PubMed] [Google Scholar]
  14. Marinetti G. V. The action of phospholipase A on lipoproteins. Biochim Biophys Acta. 1965 Jun 1;98(3):554–565. doi: 10.1016/0005-2760(65)90152-9. [DOI] [PubMed] [Google Scholar]
  15. Nowycky M. C., Sgaragli G. P., Cooper J. R., Roth R. H. Effect of collagenase on the release of dopamine and acetylcholine from slices of rat corpus striatum. J Neurochem. 1975 Jun;24(6):1279–1281. doi: 10.1111/j.1471-4159.1975.tb03914.x. [DOI] [PubMed] [Google Scholar]
  16. Oberg S. G., Kelly R. B. The mechanism of beta-bungarotoxin action. I. Modification of transmitter release at the neuromuscular junction. J Neurobiol. 1976 Mar;7(2):129–141. doi: 10.1002/neu.480070206. [DOI] [PubMed] [Google Scholar]
  17. ROSENTHAL A. F., GEYER R. P. A synthetic inhibitor of venom lecithinase A. J Biol Chem. 1960 Aug;235:2202–2206. [PubMed] [Google Scholar]
  18. Roskoski R., Jr Choline acetyltransferase. Evidence for an acetyl-enzyme reaction intermediate. Biochemistry. 1973 Sep 11;12(19):3709–3714. doi: 10.1021/bi00743a021. [DOI] [PubMed] [Google Scholar]
  19. Sen I., Cooper J. R. The effect of beta-gungarotoxin on the release of acetylcholine from brain synaptosomal preparations. Biochem Pharmacol. 1975 Nov 15;24(22):2107–2109. doi: 10.1016/0006-2952(75)90113-6. [DOI] [PubMed] [Google Scholar]
  20. Sgaragli G., Cooper J. R. Effect of collagenase pretreatment on choline and acetylcholine release from slices of bovine superior cervical sympathetic ganglia. Biochem Pharmacol. 1974 Feb 15;23(4):911–916. doi: 10.1016/0006-2952(74)90222-6. [DOI] [PubMed] [Google Scholar]
  21. Simon J. R., Kuhar M. G. Impulse-flow regulation of high affinity choline uptake in brain cholinergic nerve terminals. Nature. 1975 May 8;255(5504):162–163. doi: 10.1038/255162a0. [DOI] [PubMed] [Google Scholar]
  22. Strong P. N., Goerke J., Oberg S. G., Kelly R. B. beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity. Proc Natl Acad Sci U S A. 1976 Jan;73(1):178–182. doi: 10.1073/pnas.73.1.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wernicke J. F., Oberjat T., Howard B. D. Beta-neurotoxin reduces neurotransmitter storage in brain synapses. J Neurochem. 1974 May;22(5):781–788. doi: 10.1111/j.1471-4159.1974.tb04295.x. [DOI] [PubMed] [Google Scholar]
  24. Wernicke J. F., Vanker A. D., Howard B. D. The mechanism of action of beta-bungarotoxin. J Neurochem. 1975 Oct;25(4):483–496. doi: 10.1111/j.1471-4159.1975.tb04354.x. [DOI] [PubMed] [Google Scholar]
  25. Yamamura H. I., Snyder S. H. Choline: high-affinity uptake by rat brain synaptosomes. Science. 1972 Nov 10;178(4061):626–628. doi: 10.1126/science.178.4061.626. [DOI] [PubMed] [Google Scholar]

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