Activation and Inhibition of the Nicotinic Receptor: Actions of Physostigmine, Pyridostigmine and Meproadifen

  • E. X. Albuquerque
  • C. N. Allen
  • Y. Aracava
  • A. Akaike
  • K. P. Shaw
  • D. L. Rickett
Part of the Advances in Behavioral Biology book series (ABBI, volume 30)


The acetylcholine receptor-ionic channnel complex (AChR) is a membrane bound glycoprotein with a molecular weight of about 250,000 daltons (23, 26) that links chemical recognition to the opening of cation channels. The AChR extends from about 50 Å on the extracellular side of the membrane and has a cytoplasmic tail of 15 Å (19, 27). The clusters of these receptors at the muscle endplate assure transmission of the signal from the nerve terminal to the postsynaptic region on the muscle fiber such that the fiber ultimately contracts in response to nerve stimulation. A large number of studies on biochemical aspects of the nicotinic AChR have been undertaken as well as on primary structural, electronmicroscopic, neutron diffraction, and other analyses (see reviews 3, 4, 18 and 31).


Receptor Desensitization Single Channel Current Channel Open Time Single Muscle Fiber Adult Frog 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adler, M., Oliveira, A.C., Albuquerque, E.X., Mansour, N.A. and Eldefrawi, A.T. (1979): J. Gen. Physiol. 74: 129–152.CrossRefGoogle Scholar
  2. 2.
    Akaike, A., Ikeda, S.R., Brookes, N., Pascuzzo, G.J., Rickett, D.L. and Albuquerque, E.X. (1984): Mol. Pharmaco1. 25: 102–112.Google Scholar
  3. 3.
    Albuquerque, E.X. and Spivak, C.E. (1984): In Natural Products and Drug Development. Alfred Benzon Symposium (eds) P. KrogsgaardLarsen, S.B. Christensen and H. Kofod, Munksgaard, Copenhagen, pp. 301–321.Google Scholar
  4. 4.
    Albuquerque, E.X., Adler, M., Spivak, C.E. and Aguayo, L. (1980): Ann. N.Y. Acad. Sci. 358: 204–238.CrossRefGoogle Scholar
  5. 5.
    Albuquerque, E.X., Akaike, A., Shaw, K.P. and Rickett, D.L. (1984): Fund. Appl. Toxicol. 4: S27 - S33.CrossRefGoogle Scholar
  6. 6.
    Albuquerque, E.X., Kuba, K. and Daly, J. (1974): J. Pharmacol. Exp. Ther. 189: 513–524.Google Scholar
  7. 7.
    Albuquerque, E.X., Warnick, J.E., Aguayo, L.G., Ickowicz, R. K., Blaustein, M.P., Maayani, S. and Weinstein, H. (1983): In Phencyclidine and Related Arylcyclohexylamines: Present and Future Applications (eds) J.M. Kamenka, E.F. Domino and P. Geneste, pp. 579–597.Google Scholar
  8. 8.
    Allen, C.N., Akaike, A. and Albuquerque, E.X. (1984): J. Physiol (Paris) 79: 338–343.Google Scholar
  9. 9.
    Anderson, C.R. and Stevens, C.F. (1973): J. Physiol. ( London ) 235: 655–691.Google Scholar
  10. 10.
    Aracava, Y., Ikeda, S.R. and Albuquerque, E.X. (1983): Neurosci. Abs. 9: 733.Google Scholar
  11. 11.
    Arcava, Y. and Albuquerque, E.X. (1984): FEBS Letters 174: 267–274.CrossRefGoogle Scholar
  12. 12.
    Arcava, Y., Ikeda, S.R., Daly, J.W., Brookes, N. and Albuquerque, E.X. (1984): Mol. Pharmacol. 26: 304–313.Google Scholar
  13. 13.
    Fertuck, H.C. and Salpeter, M.M. (1974): Proc. Natl. Acad. Sci. USA 71: 1376–1378.CrossRefGoogle Scholar
  14. 14.
    Gardner, P., Ogden, D.C. and Colquhoun, D. (1984): Nature 309: 160–162.CrossRefGoogle Scholar
  15. 15.
    Ciller, E.L., Jr., Neale, J.H., Bullock, P.N., Schrier, B.K. and Nelson, P.G. (1977): J. Cell Biol. 74: 16–29.CrossRefGoogle Scholar
  16. 16.
    Hamill, O.P. and Sakmann, B. (1981): Nature 294: 462–464.CrossRefGoogle Scholar
  17. 17.
    Hamill, O.P., Marty, A., Neher, E., Sakmann, B. and Sigworth, F.J. (1981): Pflugers Arch. 391: 85–100.CrossRefGoogle Scholar
  18. 18.
    Karlin, A. (1980): In The Cell Surface and Neuronal Function (eds) C.W. Cotman, G. Poste and G.L. Nicolson, Elsevier/NorthHolland Biomedical Press, pp. 191–260.Google Scholar
  19. 19.
    Klymkowsky, M.W. and Stroud, R.M. (1979): J. Mol. Biol. 128: 319–334.CrossRefGoogle Scholar
  20. 20.
    Krodel, E.K., Beckman, R.A. and Cohen, J.B. (1979): Mol. Pharmacol. 15: 294–312.Google Scholar
  21. 21.
    Kuffler, S.W. and Yoshikami, D. (1975): J. Physiol. ( London ) 251: 465–482.Google Scholar
  22. 22.
    Maleque, M.A., Souccar, C., Cohen, J.B. and Albuquerque, E.X. (1982): Mol. Pharmacol. 22: 636–647.Google Scholar
  23. 23.
    Martinez-Carrion, M., Sator, V. and Raftery, M.A. (1975): Biochem. Biophys. Res. Commun. 65: 129–137.CrossRefGoogle Scholar
  24. 24.
    Neher, E. and Sakmann, B. (1976): Nature 260: 799–801.CrossRefGoogle Scholar
  25. 25.
    Pascuzzo, G.J., Akaike, A., Maleque, M.A., Shaw, K.P., Aronstam, R.S., Rickett, D.L. and Albuquerque, E.X. (1984): Mol. Pharmacol. 25: 92–101.Google Scholar
  26. 26.
    Reynolds, J.A. and Karlin, A. (1978): Biochemistry 17: 2035–2038.CrossRefGoogle Scholar
  27. 27.
    Ross, M.J., Klymkowsky, M.W., Agard, D.A. and Stroud, R.M. (1977): J. Mol. Biol. 116: 635–659.CrossRefGoogle Scholar
  28. 28.
    Sakmann, B., Patlak, J. and Neher, E. (1980): Nature 286: 71–73.CrossRefGoogle Scholar
  29. 29.
    Shaw, K.P., Akaike, A. and Albuquerque, E.X. (1983): Neurosci. Abs. 9: 1138.Google Scholar
  30. 30.
    Sherby, S.M., Shaw, K.P., Albuquerque, E.X. and Eldefrawi, M.E. (1984): Fed. Proc. Abs. 43: 342.Google Scholar
  31. 31.
    Spivak, C.E. and Albuquerque, E.X. (1982): In Progress in Cholinergic Biology: Model Cholinergic Synapses (eds) I. Hanin and A.M. Goldberg, Raven Press, New York, pp. 323–357.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • E. X. Albuquerque
    • 1
  • C. N. Allen
    • 1
  • Y. Aracava
    • 1
  • A. Akaike
    • 1
  • K. P. Shaw
    • 1
  • D. L. Rickett
    • 2
  1. 1.Department of Pharmacology and Experimental TherapeuticsUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Medical Chemical Defense Research ProgramU.S. Army Medical Research and Development CommandFort DetrickUSA

Personalised recommendations