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Acetylcholine receptor conformational transition on excitation masks disulphide bonds against reduction

Abstract

KARLIN and Bartels1 found that dithiothreitol (DTT) inhibits the responses induced by acetylcholine (ACh) in the Electrophorus electricus electroplax preparation and that 5,5′-dithio-bis-(2-nitrobenzoic acid) completely restored the membrane sensitivity to ACh. These results illustrate the importance of disulphide bonds for acetylcholine receptor (AChR) function, and work on other preparations with nicotinic AChRs gave similar results2–9. Several facts suggest that DTT affects AChRs specifically; (1), the significance of the quaternary ammonium group in the molecules of alkylating and acylating agents for the rate of their reaction with the AChR reduced by DTT10; (2) changes in pharmacological specificity seen in the modified receptor5,7,10;(3) the decrease in the slope of the dose–response curve to carbamylcholine expressed as the Hillplot11; and (4) the increase in d-tubocurarine affinity to the AChR active site5. If we could protect the receptor against chemical modification by an agonist or antagonist, this would be the most reliable proof of the specificity of modifying agent action12. We present here a detailed study of the action of DTT on nicotinic AChRs of completely isolated Limnaea stagnalis neurones in order to clarify the ability of various cholinergic ligands to protect the receptor disulphide bonds against reduction by DTT.

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References

  1. Karlin, A. & Bartels, E. Biochim. biophys. Acta 126, 525–535 (1966).

    Article  CAS  Google Scholar 

  2. Albuquerque, E. X., Sokoll, M. D., Sonesson, B. & Thesleff, S. Eur. J. Pharmac. 4, 40–46 (1968).

    Article  CAS  Google Scholar 

  3. Mittag, T. W. & Tormay, A. Fedn Proc. 29, 574 (1970).

    Google Scholar 

  4. Del Castillo, J., Escobar, I. & Gijon, E. Int. J. Neurosci. 1, 199–209 (1971).

    Article  CAS  Google Scholar 

  5. Rang, H. P. & Ritter, J. M. Molec. Pharmac. 7, 620–631 (1971).

    CAS  Google Scholar 

  6. Eldefrawi, M. E. & Eldefrawi, A. T. Proc. natn. Acad. Sci. U.S.A. 69, 1776–1780 (1972).

    Article  ADS  CAS  Google Scholar 

  7. Ross, D. H. & Triggle, D. J. Biochem. Pharmac. 21, 2533–2536 (1972).

    Article  CAS  Google Scholar 

  8. Ben-Haim, D., Landau, E. M. & Silman, I. J. Physiol. Lond. 234, 305–325 (1973).

    Article  CAS  Google Scholar 

  9. Sato, T., Sato, M. & Sawada, M. Jap. J. Physiol. 26, 471–485 (1976).

    Article  CAS  Google Scholar 

  10. Karlin, A. & Winnik, M. Proc. natn. Acad. Sci. U.S.A. 60, 668–674 (1968).

    Article  ADS  CAS  Google Scholar 

  11. Karlin, A. J. theoret. Biol. 16, 306–320 (1967).

    Article  CAS  Google Scholar 

  12. Singer, S. J. Adv. Protein Chem. 22, 1–54 (1967).

    Article  CAS  Google Scholar 

  13. Kostenko, M. A. Cytologia 14, 1274–1279 (1 2).

  14. Kostenko, M. A., Geletyuk, V. I. & Veprintsev, B. N. Comp. Biochem. Physiol. 49A, 89–100 (1974).

    Article  CAS  Google Scholar 

  15. Silman, I. & Karlin, A. Science 164, 1420–1421 (1969).

    Article  ADS  CAS  Google Scholar 

  16. Schimerlik, M. & Raftery, M. A. Biochem. biophys. Res. Commun. 73, 607–613 (1976).

    Article  CAS  Google Scholar 

  17. Grünhagen, H. H. & Changeux, J.-P. J. molec. Biol. 106, 517–535 (1976).

    Article  Google Scholar 

  18. Bregestovski, P. D., Vulfius, C. A. & Veprintsev, B. N. in Acetylcholine Receptor Function and the Structure of its Active Site 113–139 (Pushchino, 1975).

    Google Scholar 

  19. Bartels, E., Deal, W., Karlin, A. & Mautner, H. Biochim. biophys. Acta 203, 568–571 (1970).

    Article  CAS  Google Scholar 

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BREGESTOVSKI, P., ILJIN, V., JURCHENKO, O. et al. Acetylcholine receptor conformational transition on excitation masks disulphide bonds against reduction. Nature 270, 71–73 (1977). https://doi.org/10.1038/270071a0

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