Effect of Diisopropylfluorophosphate on Synaptic Transmission and Acetylcholine Sensitivity in Neuroblastoma-Myotube Co-Culture

  • M. Adler
  • F.-C. T. Chang
  • D. Maxwell
  • G. Mark
  • J. F. Glenn
  • R. E. Foster
Part of the Advances in Behavioral Biology book series (ABBI, volume 30)

Abstract

The toxicity of organophosphorous cholinesterase inhibitors is believed to result primarily from inhibition of acetylcholinesterase (AChE) and consequent increases in acetylcholine (ACh) lifetime (10). At the vertebrate neuromuscular junction, blockade of AChE leads to increases in the amplitude and time course of spontaneous miniature endplate potentials (MEPPs), evoked endplate potentials (EPPs) and their underlying currents (7, 9, 11). In mammalian but not amphibian preparations, anticholinesterase agents also cause repetitive antidromic firing in the presynaptic axon in response to a single conditioning stimulus (12). This phenomenon has been attributed to nerve terminal depolarization due to accumulation of Ach (17) or K+ (12) in the synaptic cleft following blockade of ACh hydrolysis.

Keywords

Hydrolysis Toxicity Depression Albumin Trypsin 

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References

  1. 1.
    Adler, M., Albuquerque, E.X. and Lebeda, F.J. (1978): Mol. Pharmacol. 14:514–529.Google Scholar
  2. 2.
    Adler, M., Pascuzzo, G.J., Maxwell, D., Glenn, J.F. and Foster, R.E. (1983): Soc. for Neurosci. (Abstr) 9: 11–38.Google Scholar
  3. 3.
    Atlas, D. and Adler, M. (1981): Proc. Natl. Acad. Sci. 78: 1237–1241.CrossRefGoogle Scholar
  4. 4.
    Bradford, N.K. (1976): Anal. Biochem. 72: 248–254.CrossRefGoogle Scholar
  5. 5.
    Christian, C.N., Nelson, P.G., Peacock, J. and Nirenberg, M. (1977): Science 196: 995–998.CrossRefGoogle Scholar
  6. 6.
    Eccles, J.C. and Jaeger, J.C. (1958): Proc. Roy. Soc. Lond. B. 148: 38–56.CrossRefGoogle Scholar
  7. 7.
    Fatt, P. and Katz, B. (1952): J. Physiol. ( Lond ) 117: 109–128.Google Scholar
  8. 8.
    Karnovsky, M. and Roots, L. (1964): J. Histochem. Cytochem. 12: 219–221.CrossRefGoogle Scholar
  9. 9.
    Katz, B. and Miledi, R. (1973): J. Physiol. ( Lond ) 231: 549–574.Google Scholar
  10. 10.
    Koelle, G.B. (1975): In: The Pharmacological Basis of Therapeutics (eds) L.S. Goodman and A. Gilman, Macmillan Publishing Co., Inc., New York, pp. 445–466.Google Scholar
  11. 11.
    Kuba, K., Albuquerque, E.X., Daly, J. and Barnard, E.A. (1974): J. Pharmacol. Exp. Ther. 189: 499–512.Google Scholar
  12. 12.
    Hohlfeld, R., Sterz, R. and Peper, K. (1981): Pflugers Arch. 391: 213–218.CrossRefGoogle Scholar
  13. 13.
    Laskowski, M.B. and Dettbarn, W.D. (1979): J. Pharmacol. Exp. Ther. 210: 269–274.Google Scholar
  14. 14.
    Nelson, P.G., Christian, C.N., Daniels, M.P. Henkart,M., Bullock, P. Mullinax, D. and Nirenberg, M. (1978): Brain Res. 147: 245–259.CrossRefGoogle Scholar
  15. 15.
    Nelson, P., Christian, C. and Nirenberg, M. (1976): Proc. Natl. Acad. Sci. 73: 123–127.CrossRefGoogle Scholar
  16. 16.
    Pascuzzo, G.J., Akaike, A., Maleque, M.A., Shaw, K-P., Aronstam, R.S., Rickett, D.L. and Albuquerque, E.X. (1983): Mol. Pharmacol. 25: 92–101.Google Scholar
  17. 17.
    Riker, W.F. Jr. and Standaert, F.G. (1966): Ann. N.Y. Acad. Sci. 135: 163–176.CrossRefGoogle Scholar
  18. 18.
    Siakotos, A.N., Filbert, M. and Hester, R. (1969): Biochem. Med. 3: 1–12.CrossRefGoogle Scholar
  19. 19.
    Sugiyama, H. (1977): FEES Letters 84: 257–260.MathSciNetCrossRefGoogle Scholar
  20. 20.
    Vigny, M., Koenig, J. and Rieger, F. (1976): J. Neurochem. 27: 1347–1353.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • M. Adler
    • 1
  • F.-C. T. Chang
    • 1
  • D. Maxwell
    • 1
  • G. Mark
    • 1
  • J. F. Glenn
    • 1
  • R. E. Foster
    • 1
  1. 1.Neurotoxicology BranchUnited States Army Medical Research Institute of Chemical DefenseAberdeen Proving GroundUSA

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