Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1373–1376. doi: 10.1111/j.1476-5381.1991.tb09796.x

The spider toxin, argiotoxin636, binds to a Mg2+ site on the N-methyl-D-aspartate receptor complex.

I J Reynolds 1
PMCID: PMC1908337  PMID: 1832066

Abstract

1. The mechanism of action of the arylalkylamine spider toxin, argiotoxin636, on the N-methyl-D-aspartate (NMDA) receptor was investigated by use of [3H]-dizocilpine binding to well-washed membranes obtained from rat brain. 2. Argiotoxin636 decreased [3H]-dizocilpine binding with an apparent potency of about 3 microM. The inhibition of [3H]-dizocilpine by argiotoxin636 was insensitive to the concentration of glutamate, glycine and spermidine in the assay. 3. Argiotoxin636 alone had no effect on the dissociation of [3H]-dizocilpine. However, argiotoxin636 reversed the actions of Mg2+ on the dissociation of [3H]-dizocilpine by decreasing the apparent potency of Mg2+. Argiotoxin636 also reversed the action of Ca2+ on the dissociation of [3H]-dizocilpine. 4. These results suggest that argiotoxin636 exerts a novel inhibitory effect on the NMDA receptor complex by binding to one of the Mg2+ sites located within the NMDA-operated ion channel.

Full text

PDF
1373

Selected References

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

  1. Adams M. E., Carney R. L., Enderlin F. E., Fu E. T., Jarema M. A., Li J. P., Miller C. A., Schooley D. A., Shapiro M. J., Venema V. J. Structures and biological activities of three synaptic antagonists from orb weaver spider venom. Biochem Biophys Res Commun. 1987 Oct 29;148(2):678–683. doi: 10.1016/0006-291x(87)90930-2. [DOI] [PubMed] [Google Scholar]
  2. Akaike N., Kawai N., Kiskin N. I., Kljuchko E. M., Krishtal O. A., Tsyndrenko AYa Spider toxin blocks excitatory amino acid responses in isolated hippocampal pyramidal neurons. Neurosci Lett. 1987 Aug 31;79(3):326–330. doi: 10.1016/0304-3940(87)90453-8. [DOI] [PubMed] [Google Scholar]
  3. Bonhaus D. W., McNamara J. O. N-methyl-D-aspartate receptor regulation of uncompetitive antagonist binding in rat brain membranes: kinetic analysis. Mol Pharmacol. 1988 Sep;34(3):250–255. [PubMed] [Google Scholar]
  4. Collingridge G. L., Lester R. A. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev. 1989 Jun;41(2):143–210. [PubMed] [Google Scholar]
  5. Foster A. C., Wong E. H. The novel anticonvulsant MK-801 binds to the activated state of the N-methyl-D-aspartate receptor in rat brain. Br J Pharmacol. 1987 Jun;91(2):403–409. doi: 10.1111/j.1476-5381.1987.tb10295.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jackson H., Parks T. N. Spider toxins: recent applications in neurobiology. Annu Rev Neurosci. 1989;12:405–414. doi: 10.1146/annurev.ne.12.030189.002201. [DOI] [PubMed] [Google Scholar]
  7. Jackson H., Usherwood P. N. Spider toxins as tools for dissecting elements of excitatory amino acid transmission. Trends Neurosci. 1988 Jun;11(6):278–283. doi: 10.1016/0166-2236(88)90112-9. [DOI] [PubMed] [Google Scholar]
  8. Johnson J. W., Ascher P. Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels. Biophys J. 1990 May;57(5):1085–1090. doi: 10.1016/S0006-3495(90)82626-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marvizón J. C., Skolnick P. [3H]glycine binding is modulated by Mg2+ and other ligands of the NMDA receptor-cation channel complex. Eur J Pharmacol. 1988 Jun 22;151(1):157–158. doi: 10.1016/0014-2999(88)90709-1. [DOI] [PubMed] [Google Scholar]
  10. Mayer M. L., Westbrook G. L., Guthrie P. B. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature. 1984 May 17;309(5965):261–263. doi: 10.1038/309261a0. [DOI] [PubMed] [Google Scholar]
  11. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  12. Priestley T., Woodruff G. N., Kemp J. A. Antagonism of responses to excitatory amino acids on rat cortical neurones by the spider toxin, argiotoxin636. Br J Pharmacol. 1989 Aug;97(4):1315–1323. doi: 10.1111/j.1476-5381.1989.tb12594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Quistad G. B., Suwanrumpha S., Jarema M. A., Shapiro M. J., Skinner W. S., Jamieson G. C., Lui A., Fu E. W. Structures of paralytic acylpolyamines from the spider Agelenopsis aperta. Biochem Biophys Res Commun. 1990 May 31;169(1):51–56. doi: 10.1016/0006-291x(90)91431-q. [DOI] [PubMed] [Google Scholar]
  14. Ransom R. W., Stec N. L. Cooperative modulation of [3H]MK-801 binding to the N-methyl-D-aspartate receptor-ion channel complex by L-glutamate, glycine, and polyamines. J Neurochem. 1988 Sep;51(3):830–836. doi: 10.1111/j.1471-4159.1988.tb01818.x. [DOI] [PubMed] [Google Scholar]
  15. Reynolds I. J. Arcaine is a competitive antagonist of the polyamine site on the NMDA receptor. Eur J Pharmacol. 1990 Feb 27;177(3):215–216. doi: 10.1016/0014-2999(90)90274-a. [DOI] [PubMed] [Google Scholar]
  16. Reynolds I. J. Arcaine uncovers dual interactions of polyamines with the N-methyl-D-aspartate receptor. J Pharmacol Exp Ther. 1990 Dec;255(3):1001–1007. [PubMed] [Google Scholar]
  17. Reynolds I. J., Miller R. J. Ifenprodil is a novel type of N-methyl-D-aspartate receptor antagonist: interaction with polyamines. Mol Pharmacol. 1989 Nov;36(5):758–765. [PubMed] [Google Scholar]
  18. Reynolds I. J., Miller R. J. Multiple sites for the regulation of the N-methyl-D-aspartate receptor. Mol Pharmacol. 1988 Jun;33(6):581–584. [PubMed] [Google Scholar]
  19. Reynolds I. J., Murphy S. N., Miller R. J. 3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7744–7748. doi: 10.1073/pnas.84.21.7744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saito M., Kawai N., Miwa A., Pan-Hou H., Yoshioka M. Spider toxin (JSTX) blocks glutamate synapse in hippocampal pyramidal neurons. Brain Res. 1985 Nov 4;346(2):397–399. doi: 10.1016/0006-8993(85)90878-9. [DOI] [PubMed] [Google Scholar]
  21. Shinozaki H. Pharmacology of the glutamate receptor. Prog Neurobiol. 1988;30(5):399–435. doi: 10.1016/0301-0082(88)90009-3. [DOI] [PubMed] [Google Scholar]
  22. Williams K., Romano C., Molinoff P. B. Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. Mol Pharmacol. 1989 Oct;36(4):575–581. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES