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. 1977 Dec;74(12):5754–5758. doi: 10.1073/pnas.74.12.5754

Histrionicotoxin enhances agonist-induced desensitization of acetylcholine receptor.

W Burgermeister, W A Catterall, B Witkop
PMCID: PMC431872  PMID: 272000

Abstract

Dihydroisohistrionicotoxin inhibits acetylcholine receptor-dependent 22Na+ uptake of cultured chick muscle cells with a KI of 0.2 micrometer. The inhibition is noncompetitive with respect to agonists. The toxin enhances desensitization of the receptor by agonists which is accompanied by a 10-fold increase in receptor affinity for agonists. Dihydroisohistrionicotoxin increases the affinity of the desensitized form of the receptor for agonists but not antagonists. The results suggest that dihydroisohistrionicotoxin inhibits the acetylcholine receptor by causing an increase in the affinity of the desensitized form of the receptor for agonists and thereby stabilizing the desensitized state.

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Selected References

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  1. Albuquerque E. X., Barnard E. A., Chiu T. H., Lapa A. J., Dolly J. O., Jansson S. E., Daly J., Witkop B. Acetylcholine receptor and ion conductance modulator sites at the murine neuromuscular junction: evidence from specific toxin reactions. Proc Natl Acad Sci U S A. 1973 Mar;70(3):949–953. doi: 10.1073/pnas.70.3.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Catterall W. A., Nirenberg M. Sodium uptake associated with activation of action potential ionophores of cultured neuroblastoma and muscle cells. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3759–3763. doi: 10.1073/pnas.70.12.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Catterall W. A. Sodium transport by the acetylcholine receptor of cultured muscle cells. J Biol Chem. 1975 Mar 10;250(5):1776–1781. [PubMed] [Google Scholar]
  4. Daly J. W., Karle I., Myers C. W., Tokuyama T., Waters J. A., Witkop B. Histrionicotoxins: roentgen-ray analysis of the novel allenic and acetylenie spiroalkaloids isolated from a Colombian frog, Dendrobates histrionicus. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1870–1875. doi: 10.1073/pnas.68.8.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dolly J. O., Albuquerque E. X., Sarvey J., Mallick B., Barnard E. A. Binding of perhydro-histrionicotoxin to the postsynaptic membrane of skeletal muscle in relation to its blockage of acetylcholine-induced depolarization. Mol Pharmacol. 1977 Jan;13(1):1–14. [PubMed] [Google Scholar]
  6. Eldefrawi A. T., Eldefrawi M. E., Albuquerque E. X., Oliveira A. C., Mansour N., Adler M., Daly J. W., Brown G. B., Burgermeister W., Witkop B. Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc Natl Acad Sci U S A. 1977 May;74(5):2172–2176. doi: 10.1073/pnas.74.5.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elliot J., Raftery M. A. Interactions of perhydrohistrionicotoxin with postsynaptic membranes. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1347–1353. doi: 10.1016/s0006-291x(77)80127-7. [DOI] [PubMed] [Google Scholar]
  8. Fischbach G. D. Synapse formation between dissociated nerve and muscle cells in low density cell cultures. Dev Biol. 1972 Jun;28(2):407–429. doi: 10.1016/0012-1606(72)90023-1. [DOI] [PubMed] [Google Scholar]
  9. Glavinović M., Henry J. L., Kato G., Krnjević K., Puil E. Histrionicotoxin: effects on some central and peripheral excitable cells. Can J Physiol Pharmacol. 1974 Dec;52(6):1220–1226. doi: 10.1139/y74-161. [DOI] [PubMed] [Google Scholar]
  10. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kato G., Changeux J. P. Studies on the effect of histrionicotoxin on the monocellular electroplax from Electrophorus electricus and on the binding of (3H)acetylcholine to membrane fragments from Torpedo marmorata. Mol Pharmacol. 1976 Jan;12(1):92–100. [PubMed] [Google Scholar]
  12. 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]
  13. Lapa A. J., Albuquerque E. X., Sarvey J. M., Daly J., Witkop B. Effects of histrionicotoxin on the chemosensitive and electrical properties of skeletal muscle. Exp Neurol. 1975 Jun;47(3):558–580. doi: 10.1016/0014-4886(75)90088-6. [DOI] [PubMed] [Google Scholar]
  14. Manthey A. A. The effect of calcium on the desensitization of membrane receptors at the neuromuscular junction. J Gen Physiol. 1966 May;49(5):963–976. doi: 10.1085/jgp.49.5.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Popot J. L., Sugiyama H., Changeux J. P. Studies on the electrogenic action of acetylcholine with Torpedo marmorata electric organ. II. The permeability response of the receptor-rich membrane fragments to cholinergic agonists in vitro. J Mol Biol. 1976 Sep 25;106(3):469–483. doi: 10.1016/0022-2836(76)90247-3. [DOI] [PubMed] [Google Scholar]
  16. Rang H. P., Ritter J. M. On the mechanism of desensitization at cholinergic receptors. Mol Pharmacol. 1970 Jul;6(4):357–382. [PubMed] [Google Scholar]
  17. Sugiyama H., Popot J. L., Changeux J. P. Studies on the electrogenic action of acetylcholine with Torpedo marmorata electric organ. III. Pharmocological desensitization in vitro of the receptor-rich membrane fragments by cholinergic agonists. J Mol Biol. 1976 Sep 25;106(3):485–496. doi: 10.1016/0022-2836(76)90248-5. [DOI] [PubMed] [Google Scholar]
  18. Vogel Z., Sytkowski A. J., Nirenberg M. W. Acetylcholine receptors of muscle grown in vitro. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3180–3184. doi: 10.1073/pnas.69.11.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weber M., David-Pfeuty T., Changeux J. P. Regulation of binding properties of the nicotinic receptor protein by cholinergic ligands in membrane fragments from Torpedo marmorata. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3443–3447. doi: 10.1073/pnas.72.9.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weiland G., Georgia B., Wee V. T., Chignell C. F., Taylor P. Ligand interactions with cholinergic receptor-enriched membranes from Torpedo: influence of agonist exposure on receptor properties. Mol Pharmacol. 1976 Nov;12(6):1091–1105. [PubMed] [Google Scholar]

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