Skip to main content
NCBI home page
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 1989 Jun;9(2):141–178. doi: 10.1007/BF00713026

Desensitization of the nicotinic acetylcholine receptor: Molecular mechanisms and effect of modulators

Enrique L M Ochoa 1, Amitabha Chattopadhyay 1, Mark G McNamee 1
PMCID: PMC11567434  PMID: 2663167

Abstract

  1. Loss of response after prolonged or repeated application of stimulus is generally termed desensitization. A wide variety of phenomena occurring in living organisms falls under this general definition of desensitization. There are two main types of desensitization processes: specific and non-specific.

  2. Desensitization of the nicotinic acetylcholine receptor is triggered by prolonged or repeated exposure to agonists and results in inactivation of its ion channel. It is a case of specific desensitization and is an intrinsic molecular property of the receptor.

  3. Desensitization of the nicotinic acetylcholine receptor at the neuromuscular junction was first reported by Katz and Thesleff in 1957. Desensitization of the receptor has been demonstrated by rapid kinetic techniques and also by the characteristic “burst kinetics” obtained from single-channel recordings of receptor activity in native as well as in reconstituted membranes. In spite of a number of studies, the detailed molecular mechanism of the nicotinic acetylcholine receptor desensitization is not known with certainty. The progress of desensitization is accompanied by an increase in affinity of the receptor for its agonist. This change in affinity is attributed to a conformational change of the receptor, as detected by spectroscopic and kinetic studies. A four-state general model is consistent with the major experimental observations.

  4. Desensitization of the nicotinic acetylcholine receptor can be potentially modulated by exogenous and endogenous substances and by covalent modifications of the receptor structure. Modulators include the noncompetitive blockers, calcium, the thymic hormone peptides (thymopoietin and thymopentin), substanceP, the calcitonin gene-related peptide, and receptor phosphorylation. Phosphorylation is an important posttranslational covalent modification that is correlated with the regulation and desensitization of the receptor through various protein kinases.

  5. Although the physiological significance of desensitization of the nicotinic receptor is not yet fully understood, desensitization of receptors probably plays a significant role in the operation of the neuronal networks associated in memory and learning processes. Desensitization of the nicotinic receptor could also possibly be related to the neuromuscular disease, myasthenia gravis.

Key words: specific desensitization, nicotinic acetylcholine receptor, molecular mechanisms, affinity transitions, modulators of desensitization, noncompetitive blockers, calcium, substance P, thymic hormones, thymopoietin, thymopentin, calcitonin gene-related peptide, receptor phosphorylation, receptor methylation, myasthenia gravis

References

  1. Adams, P. R. (1975). A study of desensitization using voltage clamp.Pflugers Arch.360135–144. [DOI] [PubMed] [Google Scholar]
  2. Adams, P. R. (1981). Acetylcholine receptor kinetics.J. Membr. Biol.58161–174. [DOI] [PubMed] [Google Scholar]
  3. Ader, R. (1981).Psychoneuroimmunology, Academic Press, New York. [Google Scholar]
  4. Afar, R., Trifaro, J. M., and Quik, M. (1988). Modulation of neuronal nicotinic acetylcholine receptor function by the thymic peptide fragment thymopentin.Soc. Neurosci. Abstr.14230. [Google Scholar]
  5. Aharonov, A., Tarrab-Hazdai, R., Abramsky, O., and Fuchs, S. (1975). Immunological relationship between acetylcholine receptor and thymus: A possible significance in myasthenia gravis.Proc. Natl. Acad. Sci. USA721456–1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Akasu, T., and Karczmar, A. G. (1980). Effects of anticholinesterases and of sodium fluoride on neoromyal desensitization.Neuropharmacology19393–403. [DOI] [PubMed] [Google Scholar]
  7. Albuquerque, E. X., and Eldefrawi, A. T. (1983).Myasthenia Gravis, Champan and Hall, London. [Google Scholar]
  8. Albuquerque, E. X., Barnard, E. A., Porter, C. W., and Warnick, J. E. (1974a). The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates.Proc. Natl. Acad. Sci. USA712818–2822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Albuquerque, E. X., Kuba, K., and Daly, J. (1974b). Effect of histrionicotoxin on the ionic conductance modulator of the cholinergic receptor: A quantitative analysis of the end-plate current.J. Pharmacol. Exp. Ther.189513–524. [PubMed] [Google Scholar]
  10. Albuquerque, E. X., Rash, J. E., Mayer, R. F., and Satterfield, J. R. (1976). An electrophysiological and morphological study of the neuromuscular junction in patients with myasthenia gravis.Exp. Neurol.51536–563. [DOI] [PubMed] [Google Scholar]
  11. Albuquerque, E. X., Tsai, M.-C., Aronstam, R. S., Witkop, B., Eldefrawi, A. T., and Eldefrawi, M. E. (1980a). Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane.Proc. Natl. Acad. Sci. USA771224–1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Albuquerque, E. X., Tsai, M.-C., Aronstam, R. S., Eldefrawi, A. T., and Eldefrawi, M. E. (1980b). Sites of action of phencyclidine: Interaction with the ionic channel of the nicotinic receptor.Mol. Pharmacol.18167–178. [PubMed] [Google Scholar]
  13. Albuquerque, E. X., Deshpande, S. S., Aracava, Y., Alkondon, M., and Daly, J. W. (1986). A possible involvement of cyclic AMP in the expression of desensitization of the nicotonic acetylcholine receptor.FEBS Lett.199113–120. [DOI] [PubMed] [Google Scholar]
  14. Albuquerque, E. X., Daly, J. W., and Warnick, J. E. (1988). Macromolecular sites for specific neurotoxins and drugs on chemosensitive synapses and electrical excitation in biological membranes. InIon Channels, Vol. I (T. Narashashi, Ed.), Plenum Press, New York, pp. 95–162. [DOI] [PubMed] [Google Scholar]
  15. Altstein, M., Dudai, Y., and Vogel, Z. (1984). Enkephalin degrading enzymes are present in the electric organ ofTorpedo californica.FEBS Lett.166183–188. [DOI] [PubMed] [Google Scholar]
  16. Anwyl, R., and Narahashi, T. (1980). Desensitization of the acetylcholine receptor of denervated rat soleus muscle and the effect of calcium.Br. J. Pharmacol.6991–98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Aoshima, H. (1984). A second, slower inactivation process in acetylcholine receptor-rich membrane vesicles prepared fromElectrophorus electricus.Arch. Biochem. Biophys.235312–318. [DOI] [PubMed] [Google Scholar]
  18. Aoshima, H., Cash, D. J., and Hess, G. P. (1980). Acetylcholine receptor-controlled ion flux in electroplax membrane vesicles: A minimal mechanism based on rate measurements in the millisecond to minute time region.Biochem. Biophys. Res. Commun.92896–904. [DOI] [PubMed] [Google Scholar]
  19. Aronstam, R. S., Eldefrawi, A. T., Pessah, I. N., Daly, J. W., Albuquerque, E. X., and Eldefrawi, M. E. (1981). Regulation of [3H]perhydrohistrionicotoxin binding toTorpedo ocellata electroplax by effectors of the acetylcholine receptor.J. Biol. Chem.2562843–2850. [PubMed] [Google Scholar]
  20. Audhya, T., and Goldstein, G. (1985). Thymopoietin and ubiquitin.Meth. Enzymol.116279–291. [DOI] [PubMed] [Google Scholar]
  21. Audhya, T., Schlesinger, D. H., and Goldstein, G. (1981). Complete amino acid sequences of bovine thymopoietins I, II, and III: Closely homologous polypeptides.Biochemistry206195–6200. [DOI] [PubMed] [Google Scholar]
  22. Audhya, T., Scheid, M. P., and Goldstein, G. (1984). Contrasting biological activities of thymopoietin and splenin, two closely related polypeptide products of thymus and spleen.Proc. Natl. Acad. Sci. USA812847–2849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Audhya, T., Schlesinger, D. H., and Goldstein, G. (1987). Isolation and complete amino acid sequence of human thymopoietin and splenin.Proc. Natl. Acad. Sci. USA843545–3549. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  24. Axelsson, S., and Thesleff, S. (1958). The “desensitizing” effect of acetylcholine on the mammalian motor end-plate.Acta Physiol. Scand.4315–26. [DOI] [PubMed] [Google Scholar]
  25. Barnard, E. A., Dolly, J. O., Porter, C. W., and Albuquerque, E. X. (1975). The acetylcholine receptor and the ionic conductance modulation system of skeletal muscle.Exp. Neurol.481–28. [DOI] [PubMed] [Google Scholar]
  26. Barrantes, F. J. (1976). Intrinsic fluorescence of the membrane-bound acetylcholine receptor: Its quenching by suberyldicholine.Biochem. Biophys. Res. Commun.72479–488. [DOI] [PubMed] [Google Scholar]
  27. Barrantes, F. J. (1978). Agonist-mediated changes of the acetylcholine receptor in its membrane environment.J. Mol. Biol.1241–26. [DOI] [PubMed] [Google Scholar]
  28. Barrantes, F. J. (1980). Modulation of acetylcholine receptor sites by thiol modification.Biochemistry192957–2965. [DOI] [PubMed] [Google Scholar]
  29. Barsoum, G. S., and Gaddum, J. H. (1935). The pharmacological estimation of adenosine and histamine in blood.J. Physiol.851–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Basch, R. S., and Goldstein, G. (1975). Antigenic and functional evidence for thein vitro inductive activity of thymopoietin (thymin) on thymocyte precursors.Ann. N.Y. Acad. Sci.249290–299. [DOI] [PubMed] [Google Scholar]
  31. Blanchard, S. G., Quast, U., Reed, K., Lee, T., Schimerlik, M. I., Vandlen, R., Claudio, T., Strader, C. D., Moore, H.-P. H., and Raftery, M. A. (1979). Interaction of [124I]-α-bungarotoxin with acetylcholine receptor fromTorpedo californica.Biochemistry181875–1883. [DOI] [PubMed] [Google Scholar]
  32. Bonner, R., Barrantes, F. J., and Jovin, T. M. (1976). Kinetics of agonist-induced intrinsic fluorescence changes in membrane-bound acetylcholine receptor.Nature263429–431. [DOI] [PubMed] [Google Scholar]
  33. Bouvier, M., Hausdorff, W. P., De Blasi, A., O'Dowd, B. F., Kobilka, B. K., Caron, M. G., and Lefkowitz, R. J. (1988). Removal of phosphorylation sites from theβ2-adrenergic receptor delays onset of agonist-promoted desensitization.Nature333370–373. [DOI] [PubMed] [Google Scholar]
  34. Box, R. J., and Staehelin, M. (1987). Study of the mechanism of hormone induced desensitization and internalization of beta-adrenergic receptors. InMembrane Receptors, Dynamics, and Energetics (K. W. A. Wirtz, Ed.), Plenum Press, New York, pp. 67–71. [Google Scholar]
  35. Boyd, N. D., and Cohen, J. B. (1980). Kinetics of binding of [3H]acetylcholine and [3H]-carbamoylcholine toTorpedo postsynaptic membranes: Slow conformational transitions of the cholinergic receptor.Biochemistry195344–5353. [DOI] [PubMed] [Google Scholar]
  36. Boyd, N. D., and Leeman, S. E. (1987). Multiple actions of substance P that regulate the functional properties of acetylcholine receptors of clonal rat PC12 cells.J. Physiol.38969–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Brehm, P., Moody-Corbett, F., and Kullberg, R. (1983). Functional properties of non-junctional acetylcholine receptors on innervated muscle.Biophys. J.41:67a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Brehm, P., Kullberg, R., and Moody-Corbett, F. (1984). Properties of non-junctional acetylcholine receptor channels on innervated muscle ofXenopus laevis.J. Physiol.350631–648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Briley, M. S., and Changeux, J.-P. (1978). Recovery of some functional properties of the detergent-extracted cholinergic receptor protein fromTorpedo marmorata after reintegration into a membrane environment.Eur. J. Biochem.84429–439. [DOI] [PubMed] [Google Scholar]
  40. Brown, R. H., Schweitzer, J. S., Audhya, T., Goldstein, G., and Dichter, M. A. (1986). Immunoreactive thymopoietin in the mouse central nervous system.Brain Res.381237–243. [DOI] [PubMed] [Google Scholar]
  41. Browning, M. D., Huganir, R., and Greengard, P. (1985). Protein phosphorylation and neuronal function.J. Neurochem.4511–23. [DOI] [PubMed] [Google Scholar]
  42. Cantoni, G. L., and Eastman, G. (1946). On the response of the intestine to smooth muscle stimulants.J. Pharmacol. Exp. Ther.87392–399. [PubMed] [Google Scholar]
  43. Carp, J. S., Aronstam, R. S., Witkop, B., and Albuquerque, E. X. (1983). Electrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.Proc. Ntal. Acad. Sci. USA80310–314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Cash, D. J., and Hess, G. P. (1980). Molecular mechanism of acetylcholine receptor-controlled ion translocation across cell membranes.Proc. Natl. Acad. Sci. USA77 842–846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Cash, D. J., and Subbarao, K. (1987). Desensitization of theγ-aminobutyric acid receptor from rat brain: Two distinguishable receptors on the same membrane.Biochemistry267556–7562. [DOI] [PubMed] [Google Scholar]
  46. Cash, D. J. and Subbarao, K. (1988). Different effects of pentobarbital on twoγ-aminobutyrate receptors from rat brain: Channel opening, desensitization, and an additional conformation change.Biochemistry274580–4590. [DOI] [PubMed] [Google Scholar]
  47. Castleman, B., and Norris, E. H. (1949). The pathology of the thymus gland in myasthenia gravis: A study of 35 cases.Medicine (Baltimore)2827–58. [DOI] [PubMed] [Google Scholar]
  48. Chang, H. W., and Neumann, E. (1976). Dynamic properties of isolated acetylcholine receptor proteins: Release of calcium ions caused by acetylcholine binding.Proc. Natl. Acad. Sci. USA733364–3368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Changeux, J.-P. (1981). The acetylcholine receptor: An “allosteric” membrane protein.The Harvey Lectures, Academic Press, New York, Vol. 75, pp. 85–254. [PubMed] [Google Scholar]
  50. Changeux, J.-P. (1986). Coexistence of neuronal messengers and molecular selection.Prog. Brain Res.68373–403. [DOI] [PubMed] [Google Scholar]
  51. Changeux, J.-P., and Heidmann, T. (1987). Allosteric receptors and molecular models of learning. InSynaptic Function (G. M. Edelman, W. E. Gall, and W. M. Cowan, Eds.), John Wiley & Sons, New York, pp. 549–601. [Google Scholar]
  52. Changeux, J.-P., and Revah, F. (1987). The acetylcholine receptor molecule: Allosteric sites and the ion channel.Trends Neurosci.10245–250. [Google Scholar]
  53. Changeux, J.-P., Devillers-Thiery, A., and Chemouilli, P. (1984a). Acetylcholine receptor: An allosteric protein.Science2251335–1345. [DOI] [PubMed] [Google Scholar]
  54. Changeux, J.-P., Heidmann, T., and Patte, P. (1984b). Learning by selection. InThe Biology of Learning (P. Marler and H. S. Terrance, Eds.), Springer-Verlag, New York, pp. 115–133. [Google Scholar]
  55. Changeux, J.-P., Giraudat, J., and Dennis, M. (1987). The nicotinic acetylcholine receptor: Molecular architecture of a ligand-regulated ion channel.Trends Pharmacol. Sci.8459–465. [Google Scholar]
  56. Chestnut, T. J. (1983). Two-component desensitization at the neuromuscular junction of the frog.J. Physiol.336229–241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Chestnut, T. J., and Carpenter, D. O. (1983). Two-component desensitization of three types of responses to acetylcholine inAplysia.Neurosci. Lett.39285–290. [DOI] [PubMed] [Google Scholar]
  58. Clapham, D. E., and Neher, E. (1984). Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells.J. Physiol.347255–257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Claudio, T., Ballivet, M., Patrick, J., and Heinemann, S. (1983). Nucleotide and deduced amino acid sequences ofTorpedo californica acetylcholine receptorγ subunit.Proc. Natl. Acad. Sci. USA801111–1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Claudio, T., Green, W. N., Hartman, D. S., Hayden, D., Paulson, H. L., Sigworth, F. J., Sine, S. M., and Swedlund, A. (1987). Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts.Science2381688–1694. [DOI] [PubMed] [Google Scholar]
  61. Cochrane, D. E., and Parsons, R. L. (1972). The interaction between caffeine and calcium in the desensitization of muscle postjunctional membrane receptors.J. Gen. Physiol.59437–461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Cohen, J. B., Weber, M., and Changeux, J.-P. (1974). Effects of local anesthetics and calcium on the interaction of cholinergic ligands with the nicotinic receptor protein fromTorpedo marmorata.Mol. Pharmacol.10904–932. [PubMed] [Google Scholar]
  63. Cohen, N. M., Schmidt, D. M., McGlennen, R. C., and Klein, W. L. (1983). Receptor-mediated increases in phosphatidylinositol turnover in neuron-like cell lines.J. Neurochem.40547–554. [DOI] [PubMed] [Google Scholar]
  64. Colquhoun, D., and Rang, H. P. (1976). Effects of inhibitors on the binding of iodinatedα-bungarotoxin to acetylcholine receptors in rat muscle.Mol. Pharmacol.12519–535. [PubMed] [Google Scholar]
  65. Conti-Tronconi, B. M., and Raftery, M. A. (1982). The nicotinic cholinergic receptor: Correlation of molecular structure with functional properties.Annu. Rev. Biochem.51491–530. [DOI] [PubMed] [Google Scholar]
  66. Conti-Tronconi, B. M., and Raftery, M. A. (1986). Nicotinic acetylcholine receptor contains multiple binding sites: Evidence from binding ofα-dendrotoxin.Proc. Natl. Acad. Sci. USA836646–6650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Conti-Tronconi, B. M., Dunn, S. M. J., and Raftery, M. A. (1982). Independent sites for low and high affinity for agonists onTorpedo californica acetylcholine receptor.Biochem. Biophys. Res. Commun.107123–129. [DOI] [PubMed] [Google Scholar]
  68. Covarrubias, M., Prinz, H., and Maelicke, A. (1984). Ligand-specific state transitions of the membrane-bound acetylcholine receptor.FEBS Lett169229–233. [DOI] [PubMed] [Google Scholar]
  69. Covarrubias, M., Prinz, H., Meyers, H.-W., and Maelicke, A. (1986). Equilibrium binding of cholinergic ligands to the membrane-bound acetylcholine receptor.J. Biol. Chem.26114955–14961. [PubMed] [Google Scholar]
  70. Criado, M., Hochschwender, S., Sarin, V., Fox, J. L., and Lindstrom, J. (1985). Evidence for unpredicted transmembrane domains in acetylcholine receptor subunits.Proc. Natl. Acad. Sci. USA822004–2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Dale, H. H. (1913). The effect of varying tonicity on the anaphylactic and other reactions of plain muscle.J. Pharmacol. Exp. Ther.4517–537. [Google Scholar]
  72. Daly, J. W., Karle, I., Myers, C. W., Tokuyama, T., Waters, J. A., and Witkop, B. (1971). Histrionicotoxins: Roentgen-ray analysis of the novel allenic and acetylenic spiroalkaloids isolated from a Colombian Frog,Dendrobates histrionicus.Proc. Natl. Acad. Sci. USA681870–1875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Damle, V. N., and Karlin, A. (1980). Effects of agonists and antagonists on the reactivity of the binding site disulfide in acetylcholine receptor fromTorpedo californica.Biochemistry193924–3932. [DOI] [PubMed] [Google Scholar]
  74. Del Castillo, J., and Webb, G. D. (1977). Rapid desensitization of acetylcholine receptors of eel electroplaques following iontophoretic application of agonist compounds.J. Physiol.270271–282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Devillers-Thiery, A., Giraudat, J., Bentaboulet, M., and Changeux, J.-P. (1983). Complete mRNA coding sequence of the acetylcholine bindingα-subunit ofTorpedo marmorata acetylcholine receptor: A model for the transmembrane organization of the polypeptide chain.Proc. Natl. Acad. Sci. USA802067–2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Devore, D. I., and Nastuk, W. L. (1977). Ionophore-mediated calcium influx effects on the post-synaptic muscle fibre membrane.Nature270441–443. [DOI] [PubMed] [Google Scholar]
  77. Dolly, J. O., Albuquerque, E. X., Sarvey, J. M., Mallick, B., and Barnard, E. A. (1977). Binding of perhydro-histrionicotoxin to the postsynaptic membrane of skeletal muscle in relation to its blockade of acetylcholine-induced depolarization.Mol. Pharmacol.131–14. [PubMed] [Google Scholar]
  78. Downing, J. E. G., and Role, L. W. (1987). Activators of protein kinase C enhance acetylcholine receptor desensitization in sympathetic ganglion neurons.Proc. Natl. Acad. Sci. USA847739–7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Dunn, S. M. J., and Raftery, M. A. (1982a). Activation and desensitization ofTorpedo acetylcholine receptor: Evidence for separate binding sites.Proc. Natl. Acad. Sci. USA796757–6761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Dunn, S. M. J., and Raftery, M. A. (1982b). Multiple binding sites for agonists onTorpedo californica acetylcholine receptor.Biochemistry216264–6272. [DOI] [PubMed] [Google Scholar]
  81. Dunn, S. M. J., Blanchard, S. G., and Raftery, M. A. (1980). Kinetics of carbamyl choline binding to membrane-bound acetyl choline receptor monitored by fluorescence changes of a covalently bound probe.Biochemistry195645–5652. [DOI] [PubMed] [Google Scholar]
  82. Dunn, S. M. J., Conti-Tronconi, B. M., and Raftery, M. A. (1983). Separate sites of low and high affinity for agonists onTorpedo californica acetylcholine receptor.Biochemistry222512–2518. [DOI] [PubMed] [Google Scholar]
  83. Earnest, J. P., Wang, H. H., and McNamee, M. G. (1984). Multiple binding sites for local anesthetics on reconstituted acetylcholine receptor membranes.Biochem. Biophys. Res. Commun.123862–868. [DOI] [PubMed] [Google Scholar]
  84. Earnest, J. P., Limbacher, H. P., McNamee, M. G., and Wang, H. H. (1986). Binding of local anesthetics to reconstituted acetylcholine receptors: Effect of protein surface potential.Biochemistry255809–5818. [DOI] [PubMed] [Google Scholar]
  85. Eldefrawi, M. E., Eldefrawi, A. T., Mansour, N. A., Daly, J. W., Witkop, B., and Albuquerque, E. X. (1978). Acetylcholine receptor and ionic channel ofTorpedo electroplax: Binding of perhydrohistrionicotoxin to membrane and solubilized preparations.Biochemistry175474–5484. [DOI] [PubMed] [Google Scholar]
  86. Eldefrawi, M. E., Aronstam, R. S., Bakry, N. M., Eldefrawi, A. T., and Albuquerque, E. X. (1980). Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin.Proc. Natl. Acad. Sci. USA772309–2313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Elias, S. B., and Appell, S. H. (1978). Acetylcholine receptor in myasthenia gravis: Increased affinity forα-bungarotoxin.Ann. Neurol.4 250–252. [DOI] [PubMed] [Google Scholar]
  88. Elliott, J., and Raftery, M. A. (1979). Binding of perhydrohistrionicotoxin to intact and detergent-solubilized membranes enriched in nicotinic acetylcholine receptor.Biochemistry181868–1874. [DOI] [PubMed] [Google Scholar]
  89. Epstein, M., and Racker, E. (1978). Reconstitution of carbamylcholine-dependent sodium ion flux and desensitization of the acetylcholine receptor fromTorpedo californica.J. Biol. Chem.2536660–6662. [PubMed] [Google Scholar]
  90. Eusebi, F., Molinaro, M., and Zani, B. M. (1985). Agents that activate protein kinase C reduce acetylcholine sensitivity in cultured myotubes.J. Cell Biol1001339–1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Fambrough, D. M., Drachman, D. B., and Satyamurti, S. (1973). Neuromuscular junction in myasthenia gravis: Decreased acetylcholine receptors.Science182293–295. [DOI] [PubMed] [Google Scholar]
  92. Fatt, P. (1950). The electromotive action of acetylcholine at the motor end-plate.J. Physiol.111408–422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Feltz, A., and Trautmann, A. (1982). Desensitization at the frog neuromuscular junction: A biphasic process.J. Physiol.322257–272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Fertuck, H. C., and Salpeter, M. M. (1976). Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after125I-α-bungarotoxin binding at mouse neuromuscular junctions.J. Cell Biol.69144–158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Finer-Moore, J., and Stroud, R. M. (1984). Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor.Proc. Natl. Acad. Sci. USA81155–159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Flynn, D. D., Kloog, Y., Potter, L. T., and Axelrod, J. (1982). Enzymatic methylation of the membrane-bound nicotinic acetylcholine receptor.J. Biol. Chem.2579513–9517. [PubMed] [Google Scholar]
  97. Fontaine, B., Klarsfeld, A., Hokfelt, T., and Changeux, J.-P. (1986). Calcitonin gene-related peptide, a peptide present in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes.Neurosci. Lett.7159–65. [DOI] [PubMed] [Google Scholar]
  98. Fontaine, B., Klarsfeld, A., and Changeux, J.-P. (1987). Calcitonin gene-related peptide and muscle activity regulate acetylcholine receptorα-subunit mRNA levels by distinct intracellular pathways.J. Cell Biol.1051337–1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Franke, C., Hatt, H., and Dudel, J. (1987). Liquid filament switch for ultra-fast exchanges of solutions at excised patches of synaptic membrane of cray fish muscle.Neurosci. Lett.77199–204. [DOI] [PubMed] [Google Scholar]
  100. Fuchs, S., Schmidt-Hopfeld, I., Tridente, G., and Tarrab-Hazdai, R. (1980). Thymic lymphocytes bear a surface antigen which cross-reacts with acetylcholine receptor.Nature287162–164. [DOI] [PubMed] [Google Scholar]
  101. Gage, P. W., McBurney, R. N., and Schneider, G. T. (1975). Effects of some aliphatic alcohols on the conductance change caused by a quantum of acetylcholine at the toad end-plate.J. Physiol.244409–429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Giraudat, J., Dennis, M., Heidmann, T., Chang, J.-Y., and Changeux, J.-P. (1986). Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: Serine-262 of theδ subunit is labeled by [3H]chlorpromazine.Proc. Natl. Acad. Sci. USA832719–2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Giraudat, J., Dennis, M., Heidmann, T., Haumont, P.-Y., Lederer, F., and Changeux, J.-P. (1987). Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in theβ andδ chains.Biochemistry262410–2418. [DOI] [PubMed] [Google Scholar]
  104. Goldstein, G. (1974). Isolation of bovine thymin: A polypeptide hormone of the thymus.Nature24711–14. [DOI] [PubMed] [Google Scholar]
  105. Goldstein, G. (1987). Overview of immunoregulation by thymopoietin. InImmune Regulation by Characterized Polypeptides (G. Goldstein, J.-F. Bach, and H. Wigzell, Eds.), Alan R. Liss, New York, pp. 51–59. [Google Scholar]
  106. Goldstein, G., and Hofmann, W. W. (1968). Electrophysiological changes similar to those of myasthenia gravis in rats with experimental autoimmune thymitis.J. Neurol. Neurosurg. Psychiat.31453–459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Goldstein, G., and Hofmann, W. W. (1969). Endocrine function of the thymus affecting neuromuscular transmission.Clin. Exp. Immunol.4181–189. [PMC free article] [PubMed] [Google Scholar]
  108. Goldstein, G., and Whittingham, S. (1966). Experimental autoimmune thymitis. An animal model of human myasthenia gravis.Lancet.II315–318. [DOI] [PubMed] [Google Scholar]
  109. Goldstein, G., and Schlesinger, D. H. (1975). Thymopoietin and myasthenia gravis: Neostigmine-responsive neuromuscular block produced in mice by a synthetic peptide fragment of thymopoietin.LancetII256–259. [DOI] [PubMed] [Google Scholar]
  110. Goldstein, G., Scheid, M. P., Boyse, E. A., Schlesinger, D. H., and Wauwe, J. V. (1979). A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin.Science2041309–1310. [DOI] [PubMed] [Google Scholar]
  111. Gordon, A. S., Davis, C. G., and Diamond, I. (1977a). Phosphorylation of membrane proteins at a cholinergic synapse.Proc. Natl. Acad. Sci. USA74263–267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Gordon, A. S., Davis, C. G., Milfay, D., and Diamond, I. (1977b). Phosphorylation of acetylcholine receptor by endogeneous membrane protein kinase in receptor-enriched membranes fromTorpedo californica.Nature267539–540. [DOI] [PubMed] [Google Scholar]
  113. Grassi, F., Monaco, L., and Eusebi, F. (1987). Acetylcholine receptor channel properties in rat myotubes exposed to forskolin.Biochem. Biophys. Res. Commun.1471000–1007. [DOI] [PubMed] [Google Scholar]
  114. Greengard, P. (1976). Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters.Nature260101–108. [DOI] [PubMed] [Google Scholar]
  115. Grob, D., and Namba, T. (1976). Characteristics and mechanism of neuromuscular block in myasthenia gravis.Ann. N.Y. Acad. Sci.274143–173. [DOI] [PubMed] [Google Scholar]
  116. Grunhagen, H.-H., and Changeux, J.-P. (1976). Studies on the electrogenic action of acetylcholine withTorpedo marmorata electric organ. IV. Quinacrine: A fluorescent probe for the conformational transitions of the cholinergic receptor protein in its membrane-bound state.J. Mol. Biol.106497–516. [DOI] [PubMed] [Google Scholar]
  117. Grunhagen, H. H., Iwatsubo, M., and Changeux, J.-P. (1977). Fast kinetic studies on the interaction of cholinergic agonists with the membrane-bound acetylcholine receptor fromTorpedo marmorata as revealed by quinacrine fluorescence.Eur. J. Biochem.80225–242. [DOI] [PubMed] [Google Scholar]
  118. Guy, R. J. (1984). A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations.Biophys. J.45249–261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Hamill, O. P., and Sakmann, B. (1981). Multiple conductance states of single acetylcholine receptor channels in embryonic muscle cells.Nature294462–464. [DOI] [PubMed] [Google Scholar]
  120. Hanke, W., and Breer, H. (1987). Characterization of the channel properties of a neuronal acetylcholine receptor reconstituted into planar lipid bilayers.J. Gen. Physiol.90855–879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Heidmann, T., and Changeux, J.-P. (1979). Fast kinetic studies on the interaction of a fluorescent agonist with the membrane-bound acetylcholine receptor fromTorpedo marmorata.Eur. J. Biochem.94255–279. [DOI] [PubMed] [Google Scholar]
  122. Heidmann, T., and Changeux, J.-P. (1980). Interaction of a fluorescent agonist with the membranebound acetylcholine receptor fromTorpedo marmorata in the millisecond time range: Resolution of an “intermediate” conformational transition and evidence for positive cooperative effects.Biochem. Biophys. Res. Commun.97889–896. [DOI] [PubMed] [Google Scholar]
  123. Heidmann, T., and Changeux, J.-P. (1984). Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transient open and closed ion channel conformations.Proc. Natl. Acad. Sci. USA811897–1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Heidmann, T., and Changeux, J.-P. (1986). Characterization of the transient agonist-triggered state of the acetylcholine receptor rapidly labeled by the noncompetitive blocker [3H]chlorpromazine: Additional evidence for theopen channel conformation.Biochemistry256109–6113. [DOI] [PubMed] [Google Scholar]
  125. Heidmann, T., Sobel, A., and Changeux, J.-P. (1980a). Conservation of the kinetic and allosteric properties of the acetylcholine receptor in its Na cholate soluble 9 S form: Effect of lipids.Biochem. Biophys. Res. Commun.93 127–133. [DOI] [PubMed] [Google Scholar]
  126. Heidmann, T., Sobel, A., Popot, J.-L., and Changeux, J.-P. (1980b). Reconstitution of a functional acetylcholine receptor.Eur. J. Biochem.11035–55. [DOI] [PubMed] [Google Scholar]
  127. Heidmann, T., Bernhardt, J., Neumann, E., and Changeux, J.-P. (1983a). Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes fromTorpedo marmorata.Biochemistry225452–5459. [DOI] [PubMed] [Google Scholar]
  128. Heidmann, T., Oswald, R. E., and Changeux, J.-P. (1983b). Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments fromTorpedo marmorata.Biochemistry223112–3127. [DOI] [PubMed] [Google Scholar]
  129. Herz, J. M., Johnson, D. A., and Taylor, P. (1987). Interaction of noncompetitive inhibitors with the acetylcholine receptor.J. Biol. Chem.2627238–7247. [PubMed] [Google Scholar]
  130. Hess, G. P., Cash, D. H., and Aoshima, H. (1979). Acetylcholine receptor-controlled ion fluxes in membrane vesicles investigated by fast reaction techniques.Nature282329–331. [DOI] [PubMed] [Google Scholar]
  131. Hess, G. P., Pasquale, E. B., Walker, J. W., and McNamee, M. G. (1982). Comparison of acetylcholine receptor-controlled cation flux in membrane vesicles fromTorpedo californica andElectrophorus electricus: Chemical kinetic measurements in the millisecond region.Proc. Natl. Acad. Sci. USA79963–967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  132. Hess, G. P., Cash, D. J., and Aoshima, H. (1983). Acetylcholine receptor-controlled ion translocation: Chemical kinetics investigations of the mechanism.Annu. Rev. Biophys. Bioeng.12443–473. [DOI] [PubMed] [Google Scholar]
  133. Higgins, L. S., and Berg, D. K. (1988). A desensitized form of neuronal acetylcholine receptor detected by3H-Nicotine binding on bovine adrenal chromaffin cells.J. Neurosci.81436–1446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  134. Hokfelt, T., Johansson, O., Ljungdahl, A., Lundberg, J. M., and Schultzberg, M. (1980). Peptidergic neurones.Nature284515–521. [DOI] [PubMed] [Google Scholar]
  135. Hokfelt, T., Holets, V. R., Staines, W., Meister, B., Melander, T., Schalling, M., Schultzberg, M., Freedman, J., Bjorklund, H., Olson, L., Lindh, B., Elfvin, L.-G., Lundberg, J. M., Lindgren, J. A., Samuelsson, B., Pernow, B., Terenius, L., Post, C., Everitt, B., and Goldstein, M. (1986). Coexistence of neuronal messengers—An overview.Prog. Brain Res.68 33–70. [DOI] [PubMed] [Google Scholar]
  136. Hucho, F. (1986). The nicotinic acetylcholine receptor and its ion channel.Eur. J. Biochem.158211–226. [DOI] [PubMed] [Google Scholar]
  137. Huganir, R. L., and Greengard, P. (1983). cAMP-dependent protein kinase phosphorylates the nicotinic acetylcholine receptor.Proc. Natl. Acad. Sci. USA801130–1134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  138. Huganir, R. L., and Greengard, P. (1987). Regulation of receptor function by protein phosphorylation.Trends Pharmacol. Sci.8472–477. [Google Scholar]
  139. Huganir, R. L., Albert, K. A., and Greengard, P (1983). Phosphorylation of the nicotinic acetylcholine receptor by Ca2+/phospholipid-dependent protein kinase, and comparison with its phosphorylation by cAMP-dependent protein kinase.Soc. Neurosci. Abstr.9578 (abstr. 168.8). [Google Scholar]
  140. Huganir, R. L., Miles, K., and Greengard, P. (1984). Phosphorylation of the nicotinic acetylcholine receptor by an endogenous tyrosine-specific protein kinase.Proc. Natl. Acad. Sci. USA816968–6972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. Huganir, R. L., Delcour, A. H., Greengard, P., and Hess, G. P. (1986). Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization.Nature321774–776. [DOI] [PubMed] [Google Scholar]
  142. Jackson, M. B. (1984). Spontaneous openings of the acetylcholine receptor channel.Proc. Natl. Acad. Sci. USA813901–3904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  143. Jackson, B. B. (1986). Kinetics of unliganded acetylcholine receptor channel gating.Biophys. J.49663–672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  144. Junge, D. (1981).Nerve and Muscle Excitation, Sinauer, Sunderland, Mass. [Google Scholar]
  145. Jurss, R., Prinz, H., and Maelicke, A. (1979). NBD-5-acetylcholine: Fluorescent analog of acetylcholine and agonist at the neuromuscular junction.Proc. Natl. Acad. Sci. USA761064–1068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Kandel, E. R., Klein, M., Hochner, B., Shuster, M., Siegelbaum, S. A., Hawkins, R. D., Glanzman, D. L., Castellucci, V. F., and Abrams, T. W. (1987). Synaptic modulation and learning: New insights into synaptic transmission from the study of behavior. InSynaptic Function (G. M. Edelman, W. E. Gall, and W. M. Cowan, Eds.), John Wiley & Sons, New York, pp. 471–518. [Google Scholar]
  147. Kaneda, N., Tanaka, F., Kohno, M., Hayashi, K., and Yagi, K. (1982). Change in the intrinsic fluorescence of acetylcholine receptor purified fromNarke japonica upon binding with cholinergic ligands.Arch. Biochem. Biophys.218376–383. [DOI] [PubMed] [Google Scholar]
  148. Kao, I., and Drachman, D. B. (1977). Thymic muscle cells bear acetylcholine receptors: Possible relation to myasthenia gravis.Science19574–75. [DOI] [PubMed] [Google Scholar]
  149. Karlin, A. (1967). On the application of “a plausible model” of allosteric proteins to the receptor for acetylcholine.J. Theor. Biol.16306–320. [DOI] [PubMed] [Google Scholar]
  150. Karlin, A. (1980). Molecular properties of nicotinic acetylcholine receptors. InThe Cell Surface and Neuronal Function (C. W. Cotman, G. Poste, and G. L. Nicolson, Eds.), Elsevier/North-Holland, Amsterdam, pp. 191–260. [Google Scholar]
  151. Karpen, J. W., and Hess, G. P. (1986). Cocaine, phencyclidine, and procaine inhibition of the acetylcholine receptor: Characterization of the binding site by stopped-flow measurements of receptor-controlled ion flux in membrane vesicles.Biochemistry251777–1785. [DOI] [PubMed] [Google Scholar]
  152. Katz, B., and Thesleff, S. (1957). A study of the “Desensitization” produced by acetylcholine at the motor end-plate.J. Physiol.13863–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  153. Kent, R. S., De Lean, A., and Lefkowitz, R. J. (1980). A Quantitative analysis of beta-adrenergic receptor interactions: Resolution of high and low affinity states of the receptor by computer modeling of ligand binding data.Mol. Pharmacol.1714–23. [PubMed] [Google Scholar]
  154. Kim, K. C., and Karczmar, A. G. (1967). Adaptation of the neuromuscular junction to constant concentration of ACh.Int. J. Neuropharmacol.651–61. [DOI] [PubMed] [Google Scholar]
  155. Kiskin, N. I., Krishtal, O. A., and Tsyndrenko, A. Y. (1986). Excitatory amino acid receptors in hippocampal neurons: Kainate fails to desensitize them.Neurosci. Lett.63225–230. [DOI] [PubMed] [Google Scholar]
  156. Klarsfeld, A., and Changeux, J.-P. (1985). Activity regulates the levels of acetylcholine receptorα-subunit mRNA in cultured chicked myotubes.Proc. Natl. Acad. Sci. USA824562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  157. Kloog, Y., Flynn, D., Hoffman, A. R., and Axelrod, J. (1980). Enzymatic carboxymethylation of the nicotinic acetylcholine receptor.Biochem. Biophys. Res. Commun.971474–1480. [DOI] [PubMed] [Google Scholar]
  158. Kobayashi, S., and Aoshima, H. (1986). Time course of the induction of acetylcholine receptors inXenopus oocytes injected with mRNA fromElectrophorus electricus electroplax.Brain Res.389211–216. [DOI] [PubMed] [Google Scholar]
  159. Komuro, K., Goldstein, G., and Boyse, E. A. (1975). Thymus-repopulating capacity of cells that can be induced to differentiate to T cellsin vitro.J. Immunol.115195–198. [PubMed] [Google Scholar]
  160. Koshland, D. E. (1981). Biochemistry of sensing and adaptation in a simple bacterial system.Annu. Rev. Biochem.50765–782. [DOI] [PubMed] [Google Scholar]
  161. Koshland, D. E. (1988). Chemotaxis as a model second-messenger system.Biochemistry275829–5834. [DOI] [PubMed] [Google Scholar]
  162. Krodel, E. K., Beckman, R. A., and Cohen, J. B. (1979). Identification of a local anesthetic binding site in nicotinic postsynaptic membranes isolated fromTorpedo marmorata electric tissue.Mol. Pharmacol.15294–312. [PubMed] [Google Scholar]
  163. Kuba, K, and Koketsu, K. (1976). Decrease of Na+ during desensitization of the frog end plate.Nature262504–505. [DOI] [PubMed] [Google Scholar]
  164. Kuhn, H. (1974). Light-dependent phosphorylation of rhodopsin in living frogs.Nature250588–590. [DOI] [PubMed] [Google Scholar]
  165. Labarca, P., Lindstrom, J., and Montal, M. (1984). Acetylcholine receptor in planar lipid bilayers.J. Gen. Physiol.83473–496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  166. Lambert, D. H., and Parsons, R. L. (1970). Influence of polyvalent cations on the activation of muscle end plate receptors.J. Gen. Physiol.56309–321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  167. Large, T. H., Lambert, M. P., Cohen, N. M., and Klein, W. L. (1986). Autonomous control of phosphatidylinositol turnover by histamine and acetylcholine receptors in the N1E-115 Neuronlike cell line.Neurosci. Lett.6631–38. [DOI] [PubMed] [Google Scholar]
  168. Larmie, E. T., and Webb, G. D. (1973). Desensitization in the electroplax.J. Gen. Physiol.61263. [Google Scholar]
  169. Lee, C. Y., Tseng, L. F., and Chiu, T. H. (1967). Influence of denervation on localization of neurotoxins from clapid venoms in rat diaphragm.Nature2151177–1178. [DOI] [PubMed] [Google Scholar]
  170. Lee, T., Witzemann, V., Schimerlik, M., and Raftery, M. A. (1977). Cholinergic ligand-induced affinity changes inTorpedo californica acetylcholine receptor.Arch. Biochem. Biophys.18357–63. [DOI] [PubMed] [Google Scholar]
  171. Lentz, T. L., Hawrot, E., and Wilson, P. T. (1987). Synthetic peptides corresponding to sequences of snake venom neurotoxins and rabies virus glycoprotein bind to the nicotinic acetylcholine receptor.Proteins Struct. Funct. Genet.2298–307. [DOI] [PubMed] [Google Scholar]
  172. Lester, H. A., Changeux, J.-P., and Sheridan, R. E. (1975). Conductance increases produced by bath application of cholinergic agonists toElectrophorus electroplaques.J. Gen. Physiol.65797–816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  173. Levitzki, A. (1984).Receptors, a Quantitative Approach, Benjamin/Cummings, Menlo Park, Calif., pp. 91–101. [Google Scholar]
  174. Levitzki, A. (1986). Bacterial adaptation, visual adaptation, receptor desensitization—a common link?Trends Pharmacol. Sci.73–6. [Google Scholar]
  175. Lindstrom, J. (1985). Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and Lambert-Eaton syndrome.Annu. Rev. Immunol.3109–131. [DOI] [PubMed] [Google Scholar]
  176. Lukas, R. J., Morimoto, H. and Bennett, E. L. (1979). Effects of thio-group modification and Ca2+ on agonist-specific state transitions of a central nicotinic acetylcholine receptor.Biochemistry182384–2395. [DOI] [PubMed] [Google Scholar]
  177. Magazanik, L. G., and Vyskocil, F. (1970). Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium.J. Physiol.210507–518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  178. Magazanik, L. G., and Vyskocil, F. (1975). The effect of temperature on desensitization kinetics at the post-synaptic membrane of the frog muscle fibre.J. Physiol.249285–300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  179. Magazanik, L. G., and Vyskocil, F. (1976). Desensitization at the neuromuscular junction. InMotor Innervation of Muscle (S. Thesleff, Ed.), Academic Press, London, pp. 151–176. [Google Scholar]
  180. Magleby, K. L., and Pallotta, B. S. (1981). A study of desensitization of acetylcholine receptors using nerve-released transmitters in the frog.J. Physiol.316225–250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  181. Malaise, M. G., Hazee-Hagelstein, M. T., Reuter, A. S., Vrinds-Gevaert, Y., Goldstein, G., and Franchimont, P. (1987). Thymopoietin and thymopentic enhance the levels of ACTH,β-endorphin, andβ-lipotropin from rat pituitary cellsin vitro.Acta Endocrinol.115455–460. [DOI] [PubMed] [Google Scholar]
  182. Manthey, A. A. (1966). The effect of calcium on the desensitization of membrane receptors at the neuromuscular junction.J. Gen. Physiol.49963–976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  183. Manthey, A. A. (1970). Further studies of the effect of calcium on the time course of action of carbamylcholine at the neuromuscular junction.J. Gen. Physiol.56407–419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  184. Manthey, A. A. (1972). The antagonistic effects of calcium and potassium on the time course of action of carbamylcholine at the neuromuscular junction.J. Membr. Biol.9319–340. [PubMed] [Google Scholar]
  185. Manthey, A. A. (1974). Changes in Ca permeability of muscle fibers during desensitization to carbamylcholine.Am. J. Physiol.226481–489. [DOI] [PubMed] [Google Scholar]
  186. McArdle, J. J. (1983). Molecular aspects of the trophic influence of nerve on muscle.Prog. Neurobiol.21135–198. [DOI] [PubMed] [Google Scholar]
  187. McArdle, J. J. (1984). Overview of the physiology of the neuromuscular junction. InThe Neuromuscular Junction (R. A. Brumback and J. W. Gerst, Eds.), Futura, New York, pp. 65–119. [Google Scholar]
  188. McCarthy, M. P., Earnest, J. P., Young, E. F., Choe, S., and Stroud, R. M. (1986). The molecular neurobiology of the acetylcholine receptor.Annu. Rev. Neurosci.9383–413. [DOI] [PubMed] [Google Scholar]
  189. McCrea, P. D., Popot, J.-L., and Engelman, D. M. (1987). Transmembrane topography of the nicotinic acetylcholine receptorδ subunit.EMBO J.63619–3626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  190. McCrea, P. D., Engelman, D. M., and Popot, J.-L. (1988). Topography of integral membrane proteins: Hydrophobicity Analysis vs. Immunolocalization.Trends Biochem. Sci.13289–290. [DOI] [PubMed] [Google Scholar]
  191. McNamee, M. G., and Ochoa, E. L. M. (1982). Reconstitution of acetylcholine receptor function in model membranes.Neuroscience72305–2319. [DOI] [PubMed] [Google Scholar]
  192. McNamee, M., Richardson, C., and Walker, J. (1984). Activation and inactivation kinetics ofTorpedo californica acetylcholine receptor in reconstituted membranes.Biophys. J.4518–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  193. McNamee, M. G., Jones, O. T., and Fong, T. M. (1986). Function of acetylcholine receptors in reconstituted liposomes. InIon Channel Reconstitution (C. Miller, Ed.), Plenum Press, New York, pp. 231–273. [Google Scholar]
  194. Medrano, S., Ochoa, E. L. M., and McNamee, M. G. (1987). The effect of amantadine on nicotinic acetylcholine receptor (nAchR) in reconstituted membranes.Neurochem. Int.11175–181. [DOI] [PubMed] [Google Scholar]
  195. Middleton, P., Jaramillo, F., and Schuetze, S. M. (1986). Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates.Proc. Natl. Acad. Sci. USA834967–4971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  196. Mielke, D. L., Kaldany, R.-R., Karlin, A., and Wallace, B. A. (1984). Effector-induced changes in the secondary structure of the nicotinic acetylcholine receptor.Biophys. J.45: 205a. [Google Scholar]
  197. Miledi, R. (1980). Intracellular calcium and desensitization of acetylcholine receptors.Proc. R. Soc. Lond. (Ser. B)209447–452. [DOI] [PubMed] [Google Scholar]
  198. Miles, K., Anthony, D. T., Rubin, L. L., Greengard, P., and Huganir, R. L. (1987). Regulation of nicotinic acetylcholine receptor phosphorylation in rat myotubes by forskolin and cAMP.Proc. Natl. Acad. Sci. USA846591–6595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  199. Miller, W. H., Ratliff, F., and Hartline, H. K. (1961). How cells receive stimuli.Sci. Am.205222–238. [DOI] [PubMed] [Google Scholar]
  200. Mishina, M., Kurosaki, T., Tobimatsu, T., Morimoto, Y., Noda, M., Yamamoto, T., Terao, M., Lindstrom, J., Takahashi, T., Kuno, M., and Numa, S. (1984). Expression of functional acetylcholine receptor from cloned cDNAs.Nature307604–608. [DOI] [PubMed] [Google Scholar]
  201. Monod, J., Wyman, J., and Changeux, J.-P. (1965). On the nature of allosteric transitions: A plausible model.J. Mol. Biol.1288–118. [DOI] [PubMed] [Google Scholar]
  202. Montal, M., Labarca, P., Fredkin, D. R., Suarez-Isla, B. A., and Lindstrom, J. (1984). Channel properties of the purified acetylcholine receptor fromTorpedo californica reconstituted in planar lipid bilayer membranes.Biophys. J.45165–174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  203. Montal, M., Anholt, R., and Labarca, P. (1986). The reconstituted acetylcholine receptor. InIon Channel Reconstitution (C. Miller, Ed.), Plenum Press, New York, pp. 157–204. [Google Scholar]
  204. Moore, H.-P. H., and Raftery, M. A. (1979). Ligand-induced interconversion of affinity states in membrane-bound acetylcholine receptor fromTorpedo californica. Effects of sulfhydryl and disulfide reagents.Biochemistry181907–1911. [DOI] [PubMed] [Google Scholar]
  205. Morel, E., Garabedian, B. V.-D., Raimond, F., Audhya, T. K., Goldstein, G., and Bach, J.-F. (1987). Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin.Eur. J. Immunol.171109–1113. [DOI] [PubMed] [Google Scholar]
  206. Morris, R. G. M., Kandel, E. R., and Squire, L. R. (1988). The neuroscience of learning and memory: Cells, neural circuits and behavior.Trends Neurosci.11125–127. [Google Scholar]
  207. Mukherjee, C., and Lefkowitz, R. J. (1977). Regulation of beta adrenergic receptors in isolated frog erythrocyte plasma membranes.Mol. Pharmacol.13291–303. [PubMed] [Google Scholar]
  208. Mulac-Jericevic, B., and Atassi, M. Z. (1986). Segmentα182–198 ofTorpedo californica acetylcholine receptor contains a second toxin-binding region and binds anti-receptor antibodies.FEBS Lett.19968–74. [DOI] [PubMed] [Google Scholar]
  209. Mulle, C., Benoit, P., Pinset, C., Roa, M., and Changeux, J.-P. (1988). Calcitonin gene-related peptide enhances the rate of desensitization of the nicotinic acetylcholine receptor in cultured mouse muscle cells.Proc. Natl. Acad. Sci. USA855728–5732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  210. Nastuk, W. L., and Parsons, R. L. (1970). Factors in the inactivation of postjunctional membrane receptors of frog skeletal muscle.J. Gen. Physiol.56218–249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  211. Neubig, R. R., and Cohen, J. B. (1980). Permeability control by cholinergic receptors inTorpedo postsynaptic membranes: Agonist dose-response relations measured at second and millisecond times.Biochemistry192770–2779. [DOI] [PubMed] [Google Scholar]
  212. Neubig, R. R., Boyd, N. D., and Cohen, J. B. (1982). Conformations ofTorpedo acetylcholine receptor associated with ion transport and desensitization.Biochemistry213460–3467. [DOI] [PubMed] [Google Scholar]
  213. Neumann, D., Barchan, D., Safran, A., Gershoni, J. M., and Fuchs, S. (1986a). Mapping of theα-bungarotoxin binding site within theα subunit of the acetylcholine receptor.Proc. Natl. Acad. Sci. USA833008–3011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  214. Neumann, D., Barchan, D., Fridkin, M., and Fuchs, S. (1986b). Analysis of ligand binding to the synthetic dodecapeptide 185–196 of the acetylcholine receptorα subunit.Proc. Natl. Acad. Sci. USA.839250–9253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  215. New, H. V., and Mudge, A. W. (1986). Calcitonin gene-related peptide regulates muscle acetylcholine receptor synthesis.Nature323809–811. [DOI] [PubMed] [Google Scholar]
  216. Niemi, W. D., Nastuk, W. L., Chang, W. W., Penn, A. S., and Rosenberry, T. L. (1979). Electrophysiological studies of thymectomized and nonthymectomized acetylcholine receptor-immunized animal models of myasthenia gravis.Exp. Neurol.631–27. [DOI] [PubMed] [Google Scholar]
  217. Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Kikyotani, S., Furutani, Y., Hirose, T., Takashima, H., Inayama, S., Miyata, T., and Numa, S. (1983). Structural homology ofTorpedo californica acetylcholine receptor subunits.Nature302528–532. [DOI] [PubMed] [Google Scholar]
  218. Oberthur, W., Muhn, P., Baumann, H., Lottspeich, F., Wittmann-Liebold, B., and Hucho, F. (1986). The reaction site of a non-competitive antagonist in theδ-subunit of the nicotinic acetylcholine receptor.EMBO J.51815–1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  219. O'Callahan, C. M., and Hosey, M. M. (1988). Multiple phosphorylation sites in the 165-kilodalton peptide associated with dihydropyridine-sensitive calcium channels.Biochemistry276071–6077. [DOI] [PubMed] [Google Scholar]
  220. Ochoa, E. L. M., Dalziel, A. W., and McNamee, M. G. (1983). Reconstitution of acetylcholine receptor function in lipid vesicles of defined composition.Biochim. Biophys. Acta727151–162. [DOI] [PubMed] [Google Scholar]
  221. Ochoa, E. L. M., Medrano, S., De Carlin, M. C. L., and Dilonardo, A. M. (1988). Arg-Lys-Asp-Val-Tyr (thymopentin) accelerates the cholinergic induced inactivation (desensitization) of reconstituted nicotinic receptor.Cell. Mol. Neurobiol.8325–331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  222. Olson, E. N., Glaser, L., and Merlie, J. P. (1984).α andβ subunits of the nicotinic acetylcholine receptor contain covalently bound lipid.J. Biol. Chem.2595364–5367. [PubMed] [Google Scholar]
  223. Oswald, R. E. (1983). Effects of calcium on the binding of phencyclidine to acetylcholine receptor-rich membrane fragments fromTorpedo californica electroplaque.J. Neurochem.411077–1084. [DOI] [PubMed] [Google Scholar]
  224. Oswald, R., and Changeux, J.-P. (1981). Ultraviolet light-induced labelling by noncompetitive blockers of the acetylcholine receptor fromTorpedo marmorata.Proc. Natl. Acad. Sci. USA783925–3929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  225. Oswald, R. E., Heidmann, T., and Changeux, J.-P. (1983). Multiple affinity states for noncompetitive blockers revealed by [3H]phencyclidine binding to acetylcholine receptor rich membrane fragments fromTorpedo marmorata.Biochemistry223128–3136. [DOI] [PubMed] [Google Scholar]
  226. Pagala, M. K. D., Namba, T., and Grob, D. (1981). Desensitization to acetylcholine at motor end plates in normal humans, patients with myasthenia gravis, and experimental models of myasthenia gravis.Ann. N.Y. Acad. Sci.377567–582. [DOI] [PubMed] [Google Scholar]
  227. Pagala, M. K. D., Tada, S., Namba, T., and Grob, D. (1982). Neuromuscular transmission in neonatal mice injected with serum globulin of myasthenia gravis patients.Neurology3212–17. [DOI] [PubMed] [Google Scholar]
  228. Parsons, R. L. (1969). Changes in postjunctional receptors with decamethonium and carbamylcholine.Am. J. Physiol.217805–811. [DOI] [PubMed] [Google Scholar]
  229. Parsons, R. L., Johnson, E. W., and Lambert, D. H. (1971). Effects of lanthanum and calcium on chronically denervated muscle fibers.Am. J. Physiol.220401–405. [DOI] [PubMed] [Google Scholar]
  230. Parsons, R. L., Cochrane, D. E., and Schnitzler, R. M. (1973). End-plate desensitization: Specificity of calcium.Life Sci.13459–465. [Google Scholar]
  231. Paton, W. D. M. (1961). A theory of drug action based on the rate of drug-receptor combination.Proc. Roy. Soc. Ser. B15421–69. [Google Scholar]
  232. Paton, W. D. M., and Rothschild, A. M. (1965). The changes in response and in ionic content of smooth muscle produced by acetylcholine action and by calcium deficiency.Br. J. Pharmacol.24437–448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  233. Patrick, J., and Lindstrom, J. (1973). Autoimmune response to acetylcholine receptor.Science180871–872. [DOI] [PubMed] [Google Scholar]
  234. Pedersen, S. E., Dreyer, E. B., and Cohen, J. (1986). Location of ligand-binding sites on the nicotinic acetylcholine receptorα-subunit.J. Biol. Chem.26113735–13743. [PubMed] [Google Scholar]
  235. Pelletier, G., Steinbusch, H. W. M., and Verhofstad, A. A. J. (1981). Immunoreactive substance P and Serotonin present in the same dense-core vesicles.Nature29371–72. [DOI] [PubMed] [Google Scholar]
  236. Pernow, B. (1983). Substance P.Pharmacol. Rev.3585–141. [PubMed] [Google Scholar]
  237. Prinz, H., and Maelicke, A. (1983). Interaction of cholinergic ligands withe purified acetylcholine receptor protein II. Kinetic studies.J. Biol. Chem.25810273–10282. [PubMed] [Google Scholar]
  238. Quast, U., Schimerlik, M., Lee, T., Witzemann, V., Blanchard, S., and Raftery, M. A. (1978a). Ligand-induced conformation changes inTorpedo californica membrane-bound acetylcholine receptor.Biochemistry172405–2414. [DOI] [PubMed] [Google Scholar]
  239. Quast, U., Schimerlik, M., and Raftery, M. A. (1978b). Stopped flow kinetics of carbamylcholine binding to membrane bound acetylcholine receptor.Biochem. Biophys. Res. Commun.81955–964. [DOI] [PubMed] [Google Scholar]
  240. Quast, U., Schimerlik, M. J., and Raftery, M. A. (1979). Ligand-induced changes in membrane-bound acetylcholine receptor observed by ethidium fluorescence. 2. Stopped flow studies with agonists and antagonists.Biochemistry181891–1901. [DOI] [PubMed] [Google Scholar]
  241. Ralston, S., Sarin, V., Thanh, H. L., Rivier, J., Fox, J. L., and Lindstrom, J. (1987). Synthetic peptides used to locate theα-bungarotoxin binding site and immunogenic regions onα subunits of the nicotinic acetylcholine receptor.Biochemistry263261–3266. [DOI] [PubMed] [Google Scholar]
  242. Rang, H. P., and Ritter, J. M. (1969). A new kind of drug antagonism: Evidence that agonists cause a molecular change in acetylcholine receptors.Mol. Pharmacol.5394–411. [PubMed] [Google Scholar]
  243. Rang, H. P., and Ritter, J. M. (1970a). On the mechanism of desensitization at cholinergic receptors.Mol. Pharmacol.6357–382. [PubMed] [Google Scholar]
  244. Rang, H. P., and Ritter, J. M. (1970b). The relationship between desensitization and the metaphilic effect at cholinergic receptors.Mol. Pharmacol.6383–390. [PubMed] [Google Scholar]
  245. Rash, J. E., Albuquerque, E. X., Hudson, C. S., Mayer, R. F., and Satterfield, J. R. (1976). Studies of human myasthenia gravis: Electrophysiological and ultrastructural evidence compatible with antibody attachment to the acetylcholine receptor complex.Proc. Natl. Acad. Sci. USA734584–4588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  246. Ratnam, M., Sargent, P. B., Sarin, V., Fox, J. L., Nguyen, D. L., Rivier, J., Criado, M., and Lindstrom, J. (1986a). Location of antigenic determinants on primary sequences of subunits of nicotinic acetylcholine receptor by peptide mapping.Biochemistry252621–2632. [DOI] [PubMed] [Google Scholar]
  247. Ratnam, M., Nguyen, D. L., Rivier, J., Sargent, P. B., and Lindstrom, J. (1986b). Transmembrane topography of nicotinic acetylcholine receptor: Immunochemical tests contradict theoretical predictions based on hydrophobicity profiles.Biochemistry252633–2643. [DOI] [PubMed] [Google Scholar]
  248. Revah, F., Mulle, C., Pinset, C., Audhya, T., Goldstein, G., and Changeux, J.-P. (1987). Calcium-dependent effect of the thymic polypeptide thymopoietin on the desensitization of the nicotinic acetylcholine receptor.Proc. Natl. Acad. Sci. USA843477–3481. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  249. Role, L. W. (1984). Substance P modulation of acetylcholine-induced currents in embryonic chicken sympathetic and ciliary ganglion neurons.Proc. Natl. Acad. Sci. USA812924–2928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  250. Rosenfeld, M. G., Mermod, J.-J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W. W., and Evans, R. M. (1983). Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing.Nature304129–135. [DOI] [PubMed] [Google Scholar]
  251. Rubsamen, H., Eldefrawi, A. T., Eldefrawi, M. E., and Hess, G. P. (1978). Characterization of the calcium-binding sites of the purified acetylcholine receptor and identification of the calcium-binding subunit.Biochemistry173818–3825. [DOI] [PubMed] [Google Scholar]
  252. Sakmann, B., Patlak, J., and Neher, E. (1980). Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist.Nature28671–73. [DOI] [PubMed] [Google Scholar]
  253. Sanchez, J. A., Dani, J. A., Siemen, D., and Hille, B. (1983). Block and possible agonist action of permeant organic ions at cholinergic chennels.Biophys. J.41:65a. [Google Scholar]
  254. Scheid, M. P., Goldstein, G., and Boyse, E. A. (1975). Differentiation of T cells in nude mice.Science1901211–1213.1081736 [Google Scholar]
  255. Scheid, M. P., Goldstein, G., and Boyse, E. A. (1978). The generation and regulation of lymphocyte populations.J. Exp. Med.1471727–1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  256. Schimerlik, M., Quast, U., and Raftery, M. A. (1979). Ligand-induced changes in membrane-bound acetylcholine receptor observed by ethidium fluorescence. 1. Equilibrium studies.Biochemistry181884–1890. [DOI] [PubMed] [Google Scholar]
  257. Schlesinger, D. H., and Goldstein, G. (1975). The amino acid sequence of thymopoietin II.Cell5361–365. [DOI] [PubMed] [Google Scholar]
  258. Schlesinger, D. H., Goldstein, G., Scheid, M. P., and Boyse, E. A. (1975). Chemical synthesis of a peptide fragment of thymopoietin II that induces selective T cell differentiation.Cell5367–370. [DOI] [PubMed] [Google Scholar]
  259. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandran, J., Reale, V., Glencorse, T. A., Seeburg, P. H., and Barnard, E. A. (1987). Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family.Nature328221–227. [DOI] [PubMed] [Google Scholar]
  260. Scubon-Mulieri, B., and Parsons, R. L. (1977). Desensitization and recovery at the frog neuromuscular junction.J. Gen. Physiol.69431–447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  261. Shiono, S., Takeyasu, K., Udgaonkar, J. B., Delcour, A. H., Fujita, N., and Hess, G. P. (1984). Regulatory properties of acetylcholine receptor: Evidence for two different inhibitory sites, one for acetylcholine and the other for a noncompetitive inhibitor of receptor function (procaine).Biochemistry236889–6893. [DOI] [PubMed] [Google Scholar]
  262. Simasko, S. M., Soares, J. R., and Weiland, G. A. (1985). Structure-activity relationship for substance P inhibition of carbamylcholine-stimulated22Na+ flux in neuronal (PC12) and non-neuronal (BC3Hl) cell lines.J. Pharmacol. Exp. Ther.235601–605. [PubMed] [Google Scholar]
  263. Simasko, S. M., Durkin, J. A., and Weiland, G. A. (1987). Effects of substance P on nicotinic acetylcholine receptor function in PC12 cells.J. Neurochem.49253–260. [DOI] [PubMed] [Google Scholar]
  264. Sine, S., and Taylor, P. (1979). Functional consequences of agonist-mediated state transitions in the cholinergic receptor.J. biol. Chem.2543315–3325. [PubMed] [Google Scholar]
  265. Sine, S. M., and Taylor, P. (1980). The relationship between agonist occupation and the permeability response of the cholinergic receptor revealed by bound cobraα-toxin.J. Biol. Chem.25510144–10156. [PubMed] [Google Scholar]
  266. Sine, S. M., and Taylor, P. (1981). Relationship between reversible antagonist occupancy and the functional capacity of the acetylcholine receptor.J. Biol. Chem.2566692–6699. [PubMed] [Google Scholar]
  267. Sitaramayya, A., and Liebman, P. A. (1983a). Mechanism of ATP quench of phosphodiesterase activation in rod disc membranes.J. Biol. Chem.2581205–1209. [PubMed] [Google Scholar]
  268. Sitaramayya, A., and Liebman, P. A. (1983b). Phosphorylation of rhodopsin and quenching of cyclic GMP phosphodiesterase activation by ATP at weak bleaches.J. Biol. Chem.25812106–12109. [PubMed] [Google Scholar]
  269. Smith, M. M., Merlie, J. P., and Lawrence, J. C. (1987). Regulation of phosphorylation of nicotinic acetylcholine receptors in mouse BC3Hl myocytes.Proc. Natl. Acad. Sci. USA846601–6605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  270. Spivak, C. E., and Albuquerque, E. X. (1982). Dynamic properties of the nicotinic acetylcholine receptor ionic channel complex: Activation blockade. InProgress in Cholinergic Biology:Model Cholinergic Synapses (I. Hanin and A. M. Goldberg, Eds.), Raven Press, New York, pp. 323–357. [Google Scholar]
  271. Spivak, C. E., Witkop, B., and Albuquerque, E. X. (1980). Anatoxin-a: A novel, potent agonist at the nicotinic receptor.Mol. Pharmacol.18384–394. [PubMed] [Google Scholar]
  272. Spivak, C. E., Waters, J., Witkop, B., and Albuquerque, E. X. (1983). Potencies and channel properties induced by semirigid agonists at frog nicotinic acetylcholine receptors.Mol. Pharmacol.23337–343. [PubMed] [Google Scholar]
  273. Stallcup, W. B., and Patrick, J. (1980). Substance P enhances cholinergic receptor desensitization in a clonal nerve cell line.Proc. Natl. Acad. Sci. USA77634–638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  274. Stanford, A. L. (1975).Foundations of Biophysics, Academic Press, New York, p. 7. [Google Scholar]
  275. Steinacker, A., and Highstein, S. M. (1976). Pre- and postsynaptic action of substance P at the Mauther fiber-giant fiber synapse in the hatchetfish.Brain Res.114128–133. [DOI] [PubMed] [Google Scholar]
  276. Stelzer, A., Kay, A. R., and Wong, R. K. S. (1988). GABAA-receptor function in hippocampal cells is maintained by phosphorylation factors.Science241339–341. [DOI] [PubMed] [Google Scholar]
  277. Stephenson, R. P. (1956). A modification of receptor theory.Br. J. Pharmacol.11379–393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  278. Stroud, R. M., and Finer-Moore, J. (1985). Acetylcholine receptor structure, function, and evolution.Annu. Rev. Cell. Biol.1317–351. [DOI] [PubMed] [Google Scholar]
  279. Stutman, O. (1983). Role of thymic hormones in T cell differentiation.Clin. Immunol. Allergy39–81. [Google Scholar]
  280. Suarez-Isla, B. A., and Hucho, F. (1977). Acetylcholine receptor: -SH group reactivity as indicator of conformational changes and functional states.FEBS Lett.7565–69. [DOI] [PubMed] [Google Scholar]
  281. Sugiyama, H., Popot, J.-L., and Changeux, J.-P. (1976). Studies on the electrogenic action of acetylcholine withTorpedo marmorata electric organ. III. Pharmacological desensitizationin vitro of the receptor-rich membrane fragments by cholinergic agonists.J. Mol. Biol.106485–496. [DOI] [PubMed] [Google Scholar]
  282. Sunshine, G. H., Basch, R. S., Coffey, R. G., Cohen, K. W., Goldstein, G., and Hadden, J. W. (1978). Thymopoietin enhances the allogenic response and cyclic GMP levels of mouse peripheral thymus-derived lymphocytes.J. Immunol.1201594–1599. [PubMed] [Google Scholar]
  283. Takami, K., Kawai, Y., Shiosaka, S., Lee, Y., Girgis, S., Hillyard, C. J., MacIntyre, I., Emson, P. C., and Tohyama, M. (1985a). Immunohistochemical evidence for the coexistence of calcitonin gene-related peptide- and choline acyltransferase-like immunoreactivity in neurons of the rat hypoglossal, facial, and ambiguus nuclei.Brain. Res.328386–389. [DOI] [PubMed] [Google Scholar]
  284. Takami, K., Kawai, Y., Uchida, S., Tohyama, M., Shiotani, Y., Yoshida, H., Emson, P. C., Girgis, S., Hillyard, C. J., and MacIntyre, I. (1985b). Effect of calcitonin gene-related peptide on contraction of striated muscle in the mouse.Neurosci. Lett.60227–230. [DOI] [PubMed] [Google Scholar]
  285. Takeyasu, K., Udgaonkar, J. B., and Hess, G. P. (1983). Acetylcholine receptor: Evidence for a voltage-dependent regulatory site for acetylcholine. Chemical kinetic measurements in membrane vesicles using a voltage clamp.Biochemistry225973–5978. [DOI] [PubMed] [Google Scholar]
  286. Takeyasu, K., Shiono, S., Udgaonkar, J. B., Fujita, N., and Hess, G. P. (1986). Acetylcholine receptor: Characterization of the voltage-dependent regulatory (inhibitory) site for acetylcholine in membrane vesicles fromTorpedo californica electroplax.Biochemistry251770–1776. [DOI] [PubMed] [Google Scholar]
  287. Tan, Y., and Barrantes, F. J. (1980). Fast kinetics of antagonist-acetylcholine receptor interactions: A temperature jump relaxation study.Biochem. Biophys. Res. Commun.92766–774. [DOI] [PubMed] [Google Scholar]
  288. Tank, D. W., Huganir, R. L., Greengard, P., and Webb, W. W. (1983). Patch-recorded single-channel currents of the purified and reconstitutedTorpedo acetylcholine receptor.Proc. Natl. Acad. Sci. USA805129–5133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  289. Teichberg, V. I., Sobel, A., and Changeux, J.-P. (1977).In vitro phosphorylation of the acetylcholine receptor.Nature267540–542. [DOI] [PubMed] [Google Scholar]
  290. Terrar, D. A. (1974). Influence of SKF-525A congeners, strophanthidin and tissue-culture media on desensitization in frog skeletal muscle.Br. J. Pharmacol.51259–268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  291. Thesleff, S. (1955). The mode of neuromuscular block caused by acetylcholine, nicotine, decamethonium and succinylcholine.Acta Physiol. Scand.34218–231. [DOI] [PubMed] [Google Scholar]
  292. Thesleff, S. (1959). Motor end-plate “desensitization” by repetitive nerve stimuli.J. Physiol.148659–664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  293. Thesleff, S. (1960). Effects of motor innervation on the chemical sensitivity of skeletal muscle.Physiol. Rev.40734–752. [DOI] [PubMed] [Google Scholar]
  294. Tigerstedt, R., and Bergman, P. G. (1898).Niere und Kreislauf.Skandin. Arch. Physiol.8223–271. [Google Scholar]
  295. Triggle, D. J. (1980). DesensitizationalTrends Pharmacol. Sci.1395–398. [Google Scholar]
  296. Triggle, D. J., and Triggle, C. R. (1976).Chemical Pharmacology of the Synapse, Academic Press, London, pp. 129–231. [Google Scholar]
  297. Trussell, L. O., Thio, L. L., Zorumski, C. F., and Fischbach, G. D. (1988). Rapid desensitization of glutamate receptors in vertebrate central neurons.Proc. Natl. Acad. Sci. USA852834–2838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  298. Turner, A. J., and Dowdall, M. J. (1984). The metabolism of neuropeptides.Biochem. J.222255–259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  299. Udgaonkar, J. B., and Hess, G. P. (1986). Acetylcholine receptor kinetics: Chemical kinetics.J. Membr. Biol.9393–109. [DOI] [PubMed] [Google Scholar]
  300. Udgaonkar, J. B., and Hess, G. P. (1987a). Chemical kinetic measurements of a mammalian acetylcholine receptor by a fast-reaction technique.Proc. Natl. Acad. Sci. USA848758–8762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  301. Udgaonkar, J. B., and Hess, G. P. (1987b). Isosteric regulation of the acetylcholine receptor.Trends Pharmacol. Sci.8190–192. [Google Scholar]
  302. Unwin, N., Toyoshima, C., and Kubalek, E. (1988). Arrangement of the acetylcholine receptor subunits in the resting and desensitized states, determined by cryoelectron microscopy of crystallizedTorpedo postsynaptic membranes.J. Cell Biol.1071123–1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  303. Vandlen, R. L., Wu, W. C.-S., Eisenach, J. C., and Raftery, M. A. (1979). Studies of the composition of purifiedTorpedo californica acetylcholine receptor and of its subunits.Biochemistry181845–1854. [DOI] [PubMed] [Google Scholar]
  304. Venkatasubramanian, K., Audhya, T., and Goldstein, G. (1986). Binding of thymopoietin to the acetylcholine receptor.Proc. Natl. Acad. Sci. USA833171–3174. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  305. Verdenhalven, J., Bandini, G., and Hucho, F. (1982). Acetylcholine receptor-rich membranes contain an endogenous protease regulated by peripheral membrane protein.FEBS Lett.147168–170. [DOI] [PubMed] [Google Scholar]
  306. Viamontes, G. I., Audhya, T., and Goldstein, G. (1986). Immunohistochemical localization of thymopoietin with an antiserum to synthetic cis-thymopoietin28–39.Cell. Immunol.100305–313. [DOI] [PubMed] [Google Scholar]
  307. Vincent, A. (1980). Immunology of acetylcholine receptors in relation to myasthenia gravis.Physiol. Rev.60756–824. [DOI] [PubMed] [Google Scholar]
  308. Wagoner, P. K., and Pallotta, B. S. (1988). Modulation of acetylcholine receptor desensitization by forskolin is independent of cAMP.Science2401655–1657. [DOI] [PubMed] [Google Scholar]
  309. Walker, J. W., Lukas, R. J., and McNamee, M. G. (1981a). Effects of thio-group modifications on the ion permeability control and ligand binding properties ofTorpedo californica acetylcholine receptor.Biochemistry202191–2199. [DOI] [PubMed] [Google Scholar]
  310. Walker, J. W., McNamee, M. G., Pasquale, E., Cash, D. J., and Hess, G. P. (1981b). Acetylcholine receptor inactivation inTorpedo californica electroplax membrane vesicles. Detection of two processes in the millisecond and second time regions.Biochem. Biophys. Res. Commun.10086–90. [DOI] [PubMed] [Google Scholar]
  311. Walker, J. W., Takeyasu, K., and McNamee, M. G. (1982). Activation and inactivation kinetics ofTorpedo californica acetylcholine receptor in reconstituted membranes.Biochemistry215384–5389. [DOI] [PubMed] [Google Scholar]
  312. Weber, M., and Changeux, J.-P. (1974). Binding ofNaja nigricollis [3H]α-toxin to membrane fragments fromElectrophorus andTorpedo electric organs.Mol. Pharmacol.1035–40. [PubMed] [Google Scholar]
  313. Weber, M., David-Pfeuty, T., and Changeux, J.-P. (1975). Regulation of binding properties of the nicotinic receptor protein by cholinergic ligands in membrane fragments fromTorpedo marmorata.Proc. Natl. Acad. Sci. USA723443–3447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  314. Weiland, G., and Taylor, P. (1979). Ligand specificity of state transitions in the cholinergic receptor: behavior of agonists and antagonists.Mol. Pharmacol.15197–212. [PubMed] [Google Scholar]
  315. Weiland, G., Georgia, B., Wee, V. T., Chignell, C. F., and Taylor, P. (1976). Ligand interactions with cholinergic receptor-enriched membranes fromTorpedo: influence of agonist exposure on receptor properties.Mol. Pharmacol.121091–1105. [PubMed] [Google Scholar]
  316. Weiland, G., Georgia, B., Lappi, S., Chignell, C. F., and Taylor, P. (1977). Kinetics of agonist-mediated transitions in state of the cholinergic receptor.J. Biol. Chem.2527648–7656. [PubMed] [Google Scholar]
  317. Weiland, G. A., Durkin, J. A., Henley, J. M., and Simasko, S. M. (1987). Effects of substance P on the binding of ligands to nicotinic acetylcholine receptors.Mol. Pharmacol.32625–632. [PubMed] [Google Scholar]
  318. Wilson, P. T., Lentz, T. L., and Hawrot, E. (1985). Determination of the primary amino acid sequence specifying theα-bungarotoxin binding site on theα subunit of the acetylcholine receptor fromTorpedo californica.Proc. Natl. Acad. Sci. USA828790–8794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  319. Yee, A. S., and McNamee, M. G. (1985). Effects of carboxymethylation by a purifiedTorpedo californica methylase on the functional properties of the acetylcholine receptor in reconstituted membranes.Arch. Biochem. Biophys.243349–360. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES