Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Thymopoietin, a thymic polypeptide, potently interacts at muscle and neuronal nicotinic α-bungarotoxin receptors

  • 37 Accesses

  • 6 Citations

Abstract

Current studies suggest that several distinct populations of nicotinic acetylcholine (ACh) receptors exist. One of these is the muscle-type nicotinic receptors with which neuromuscular nicotinic receptor ligands and the snake toxin α-bungarotoxin interact. α-Bungarotoxin potently binds to these nicotinic receptors and blocks their function, two characteristics that have made the α-toxin a very useful probe for the characterization of these sites. In neuronal tissues, several populations of nicotinic receptors have been identified which, although they share a nicotinic pharmacology, have unique characteristics. The α-bungarotoxin-insensitive neuronal nicotinic receptors, which may be involved in mediating neuronal excitability, bind nicotinic agonists with high affinity but do not interact with α-bungarotoxin. Subtypes of these α-toxin-insensitive receptors appear to exist, as evidenced by findings that some are inhibited by neuronal bungarotoxin whereas others are not. In addition to the α-bungarotoxin-insensitive sites, α-bungarotoxin-sensitive neuronal nicotinic receptors are also present in neuronal tissues. These latter receptors bind α-bungarotoxin with high affinity and nicotinic agonists with an affinity in the μM range. The function of the nicotinic α-bungarotoxin receptors are as yet uncertain.

Thymopoietin, a polypeptide linked to immune function, appears to interact specifically with nicotinic receptor populations that bind α-bungarotoxin. Thus, in muscle tissue where α-bungarotoxin both binds to the receptor and blocks activity, thymopoietin also potently binds to the receptor and inhibits nicotinic receptormediated function. In neuronal tissues, thymopoietin interacts only with the nicotinic α-bungarotoxin site and not the α-bungarotoxin-insensitive neuronal nicotinic receptor population. These observations that thymopoietin potently and specifically interacts with nicotinic α-bungarotoxin-sensitive receptors in neuronal and muscle tissue, together with findings that thymopoietin is an endogenously occurring agent, could suggest that this immune-related polypeptide represents a ligand for the α-bungarotoxin receptors. The function of thymopoietin at the α-bungarotoxin receptor is as yet uncertain; however, a potential trophic, as well as other roles are suggested.

This is a preview of subscription content, log in to check access.

References

  1. Abood L. G. and Grassi S. (1986) [3H] Methylcarbamylcholine, a new radioligand for studying brain nicotinic receptors.Biochem. Pharmacol. 35, 4199–4202.

  2. Alkondon M. and Albuquerque E. X. (1990) α-Cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons.Eur. J. Pharmacol. 191, 505–506.

  3. Anand R., Conroy W. G., Schoepfer R., Whiting P., and Lindstrom J. (1991) Neuronal nicotinic acetylcholine receptors expressed inXenopus oocytes have a pentameric quaternary structure.J. Biol. Chem. 17, 11,192–11,198.

  4. Arimatsu Y., Seto A., and Amano T. (1981) Sexual dimorphism in α-bungarotoxin binding capacity in the mouse amygdala.Brain Res. 213, 432–437.

  5. Audhya T., Schlesinger D. H., and Goldstein G. (1981) Complete amino acid sequences of bovine thymopoietins I, II, and III: Closely homologous polypeptides.Biochemistry 20, 6195–6200.

  6. Audhya T., Scheid M. P., and Goldstein G. (1984)a Contrasting biological activities of thymopoietin and splenin, two closely related polypeptide products of thymus and spleen.Proc. Natl. Acad. Sci. USA 81, 2847–2849.

  7. Audhya T., Heavner G. A., Kroon D. J., and Goldstein G. (1984b) Cooperativity of thymopoietin 32–36 (the active site) and thymopoietin 38–45 in receptor binding.Reg. Peptides 9, 155–164.

  8. Ballivet M., Patrick J., Lee J., and Heinemann S. (1982) Molecular cloning of cDNA coding for the gamma subunit ofTorpedo acetylcholine receptor.Neurobiology 79, 4466–4470.

  9. Ballivet M., Nef P., Couturier S., Rungger D., Bader C. R., Bertrand D., and Cooper E. (1988) Electrophysiology of a chick neuronal nicotinic acetylcholine receptor expressed inXenopus oocytes after cDNA injection.Neuron 1, 847–852.

  10. Basch R. S. and Goldstein G. (1974) Induction of T-cell differentiationin vitro by thymin, a purified polypeptide hormone of the thymus.Proc. Natl. Acad. Sci. USA 71, 1474–1478.

  11. Basch R. S. and Goldstein G. (1975) Thymopoietininduced acquisition of responsiveness to T cell mitogens.Cell Immunol. 20, 218–228.

  12. Berg D. K. and Halvorsen S. W. (1988) Genesencoding nicotinic receptor subtypes on neurons.Nature 334, 384–385.

  13. Bertrand D., Ballivet M., and Rungger D. (1990) Activation and blocking of neuronal nicotinic acetylcholine receptor reconstituted in xenopus oocytes.Proc. Nat. Acad. Sci. USA 87, 1993–1997.

  14. Betz H., Graham D., and Rehm H. (1982) Identification of polypeptides associated with a putative neuronal nicotinic acetylcholine receptor.J. Biol. Chem. 257, 11,390–11,394.

  15. Betz H. and Pfeiffer F. (1984) Monoclonal antibodies against the α-bungarotoxin binding protein of chick optic lobe.J. Neurosci. 4, 2095–2105.

  16. Boksa P. and Quirion R. (1987) [3H]N-methylcarbamylcholine, a new radioligand specific for nicotinic acetylcholine receptors in brain.Eur. J. Pharmacol. 139, 323–333.

  17. Boulter J., Evans K., Goldman D., Martin G., Treco D., Heinemann S., and Patrick J. (1986) Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor α-subunit.Nature 319, 368–374.

  18. Boulter J., Connolly J., Deneris E., Goldman D., Heinemann S., and Patrick J. (1987) Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.Proc. Natl. Acad. Sci. USA 84, 7763–7767.

  19. Boulter J., O'Shea-Greenfield A., Duvoisin R. M., Connolly J. G., Wada E., Jensen A., Gardner P. D., Ballivet M., Deneris E. S., McKinnon D., Heinemann S., and Patrick J. (1990) α3, α5 and β4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster.J. Biol. Chem. 265, 4472–4482.

  20. Brown D. A. and Fumagalli L. (1977) Dissociation of α-bungarotoxin binding and receptor block in the rat superior cervical ganglion.Brain Res. 129, 165–168.

  21. 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. 381, 237–243.

  22. Bursztajn S. and Gershon M. D. (1977) Discrimination between nicotinic receptors in vertebrate ganglia and skeletal muscle by alpha-bungarotoxin and cobra venoms.J. Physiol. (Lond) 269, 17–31.

  23. Changeux J.-P., Kasai M., and Lee C. Y. (1970) Use of a snake venom to characterize the cholinergic receptor protein.Proc. Natl. Acad. Sci. USA,67, 1241–1247.

  24. Changeux J.-P. and Revah F. (1987) The acetylcholine receptor molecule: allosteric sites and the ion channel.Trends Neurosci. 10, 245–250.

  25. Changeux J.-P., Giraudet J., and Dennis M. (1987) The nicotinic acetylcholine receptor: molecular architecture of a ligand-regulated ion channel.Trends Pharmacol. Sci. 8, 459–465.

  26. Changeux J.-P. (1990) The nicotinic acetylcholine receptor: an allosteric protein prototype of ligand-gated ion channels.Trends Pharmacol. Sci. 11, 485–492.

  27. Chiappinelli V. A. and Giacobini E. (1978) Time course of appearance of α-bungarotoxin binding sites during development of chick ciliary ganglion and iris.Neurochem. Res. 3, 465–478.

  28. Chiappinelli V. A. (1984) Kappa-bungarotoxin: a probe for the neuronal nicotinic acetylcholine receptor.Trends Pharmacol. Sci. 7, 425–428.

  29. Chini B., Clementi F., Hukovic N., and Sher E. (1991) Neuronal type α-bungarotoxin receptors and the α5 nicotinic receptor subunit gene are expressed in neuronal and non neuronal human cell lines.Proc. Nat. Acad. Sci. USA, in press.

  30. Clarke P. B. S., Schwartz R. D., Paul S. M., Pert C. B., and Pert A. (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine and [125I]α-bungarotoxin.J. Neurosci. 5, 1307–1315.

  31. Collins A. C., Evans C. B., Miner L. L., and Marks M. J. (1986) Mecamylamine blockade of nicotine responses: evidence for two brain nicotinic receptors.Pharmacol. Biochem. Behav.,24, 1767–1773.

  32. Conti-Tronconi B. M., Dunn S. M. J., Barnard E. A., Dolly J. O., Lai F. A., Ray N., and Raftery M. A. (1985) Brain and muscle nicotinic acetylcholine receptors are different but homologous proteins.Proc. Natl. Acad. Sci. USA 82, 5208–5212.

  33. Cooper E., Couturier S., and Ballivet M. (1991) Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor.nature 350, 235–238.

  34. Couturier S., Bertrand D., Matter J.-M., Hernandez M.-C., Bertrand S., Millar N., Valera S., Barkas T., and Ballivet M. (1990a) A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-BTX.Neuron 5, 847–856.

  35. Couturier S., Erkman L., Valera S., Rungger D., Bertrand S., Boulter J., Ballivet M., and Bertrand D. (1990b) α5, α3 and non-α3: three clustered avian genes encoding neuronal nicotinic acetylcholine receptor-related subunits.J. Biol. Chem. 265, 17,560–17,567.

  36. Criado M., Koenen M., and Sakmann B. (1990) Assembly of an adult type acetylcholine receptor in a mouse cell line transfected with rat muscle ε-subunit DNA.Fed. Eur. Biochem. Soc. 270, 95–99.

  37. Daniels M. P. and Vogel Z. (1980) Localization of α-bungarotoxin binding sites in synapses of the developing chick retina.Brain Res. 201, 45–46.

  38. Daubas P., Devillers-Thiéry A., Geoffroy B., Martinez S., Bessis A., and Changeux J.-P. (1990) Differential expression of the neuronal acetylcholine receptor α2 subunit gene during chick brain development.Neuron 5, 49–60.

  39. De La Garza R., McGuire T. J., Freedman R., and Hoffer B. J. (1987) Selective antagonism of nicotine actions in the rat cerebellum with α-bungarotoxin.Neuroscience 23, 887–891.

  40. Deneris E. S., Connolly J., Boulter J., Wada E., Wada K., Swanson L. W., Patrick J., and Heinemann S. (1988) Primary structure and expression of β2: a novel subunit of neuronal nicotinic acetylcholine receptors.Neuron 1, 45–54.

  41. Deneris E. S., Boulter J., Swanson L. W., Patrick J., and Heinemann S. (1989) β3: a new member of nicotinic acetylcholine receptor gene family is expressed in brain.J. Biol. Chem. 264, 6268–6272.

  42. Deneris E. S., Connolly J., Rogers S. W., and Duvoisin R. (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors.Trends Pharmacol. Sci. 12, 34–40.

  43. Deutch A. Y., Holliday J., Roth R. H., Chun L. L. Y., and Hawrot E. (1987) Immunohistochemical localization of a neuronal nicotinic acetylcholine receptor in mammalian brain.Proc. Natl. Acad. Sci. USA 84, 8697–8701.

  44. Devillers-Thiéry A., Giraudat J., Bentaboulet M., and Changeux J.-P. (1983) Complete mRNA coding sequence of the acetylcholine binding α-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain.Proc. Natl. Acad. Sci. USA 80, 2067–2071.

  45. Dolly J. O. and Barnard E. A. (1984) Nicotinic acetylcholine receptors: an overview.Biochem. Pharmacol. 33, 841–858.

  46. Duggan A. W., Hall J. G., and Lee C.-Y. (1976) α-Bungarotoxin cobra neurotoxin and excitation of Renshaw cells by acetylcholine.Brain Res. 107, 166–170.

  47. Duvoisin R. M., Deneris E. S., Patrick J., and Heinemann S. (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: β4.Neuron,3, 487–496.

  48. Falkeborn Y., Larsson C., Nordberg A., and Slanina A. (1983) A comparison of the regional onto-genesis of nicotine- and muscarine-like binding sites in mouse brain.Int. J. Dev. Neurosci. 1, 289–296.

  49. Falkeborn Y. and Lundberg P.-A. (1985) Regional [3H]acetylcholine and [3H]nicotine binding in developing mouse brain.Int. J. Dev. Neurosci. 3, 667–671.

  50. Fambrough D. M. (1979) Control of acetylcho-line receptors in skeletal muscle.Physiol. Rev. 59, 165–227.

  51. Fiedler E. P., Marks M. J., and Collins A. C. (1987) Postnatal development of cholinergic enzymes and receptors in mouse brain.J. Neurochem. 49, 983–990.

  52. Fiedler E. P., Marks M. J., and Collins A. C. (1990) Postnatal development of two nicotinic cholinergic receptors in seven mouse brain regions.Int. J. Dev. Neurosci. 8, 533–540.

  53. Fornasari D., Chini B., Tarroni P., and Clementi F. (1990) Molecular cloning of human neuronal nicotinic receptor α3-subunit.Neuroscience Lett. 111, 351–356.

  54. Freeman J. A. (1977) Possible regulatory function of acetylcholine receptor in maintenance of retinotectal synapses.Nature 269, 218–222.

  55. Fuchs J. L. and Hoppens K. S. (1987) α-Bungarotoxin binding in relation to functional organization of the rat suprachiasmatic nucleus.Brain Res. 407, 9–16.

  56. Fuchs J. L. (1989) [125I]α-Bungarotoxin binding marks primary sensory areas of developing rat neocortex.Brain Res. 501, 223–234.

  57. Galzi J.-L., Revah F., Bessis A., and Changeux J.-P. (1991) Functional architecture of the nicotinic acetylcholine receptor: from electric organ to brain.Ann. Rev. Pharmacol. 31, 37–72.

  58. Geertsen S., Afar R., Trifaró J.-M., and Quik M. (1988) Regulation of α-bungarotoxin sites in chromaffin cells in culture by nicotinic receptor ligands, K+ and cAMP.Mol. Pharmacol. 34, 549–556.

  59. Goldman D., Deneris E., Luyten W., Kochhar A., Patrick J., and Heinemann S. (1987) Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system.Cell 48, 965–973.

  60. Goldstein G. (1966) Thymitis and myasthenia gravis.Lancet II, 1164–1167.

  61. Goldstein G. (1968) The thymus and neuromuscular function: a substance in thymus which causes myositis and myasthenic neuromuscular block in guinea pigs.Lancet II, 119–122.

  62. 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. 31, 453–459.

  63. Goldstein G. (1971) Thymin: a thymic polypeptide causing the neuromuscular block of myasthenia gravis.Ann. NY Acad. Sci. 183, 230–240.

  64. Goldstein G. (1974) Isolation of bovine thymin: a polypeptide hormone of the thymus.Nature 247, 11–14.

  65. Goldstein G., Scheid M., Hammerling U., Boyse E. A., Schlesinger D. H., and Niall H. D. (1975) Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells.Proc. Natl. Acad. Sci. USA 72, 11–15.

  66. 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.Science 204, 1309,1310.

  67. Goldstein G. (1987) Overview of immunoregulation by thymopoietin.Immune Regulation by Characterized Polypeptides, 51–59.

  68. Gotti C., Omini C., Berti F., and Clementi F. (1985) Isolation of a polypeptide from the venom ofBungarus multicinctus that binds to ganglia and blocks ganglionic transmission in mammals.Neuroscience 15, 563–575.

  69. Gotti C., Esparis-Ogando A., and Clementi F. (1989) The α-bungarotoxin receptor purified from a human neuroblastoma cell line: biochemical and immunological characterization.Neuroscience 32, 759–767.

  70. Gotti C., Esparis-Ogando A., Hanke W., Schlue R., Moretti M., and Clementi F. (1991) Purification and characterization of an α-bungarotoxin receptor that forms a functional nicotinic channel.Proc. Natl. Acad. Sci. USA 88, 3258–3262.

  71. Guy H. R. and Hucho F. (1987) The ion channel of the nicotinic acetylcholine receptor.Trends Neurosci. 10, 318–321.

  72. Hartman S. H. and Claudio T. (1990) Coexpression of two distinct muscle acetylcholine receptor α-subunits during development.Nature 343, 372–375.

  73. Jackson M. B., Imoto K., Mishina M., Konno T., Numa S., and Sakmann B. (1990) Spontaneous and agonist-induced openings of an acetylcholine receptor channel composed of bovine muscle α-, β- and δ-subunits.Pflügers Arch. 417, 129–135.

  74. Jacob M. H. and Berg D. K. (1983) The ultrastructural localization of α-bungarotoxin binding sites in relation to synapses on chick ciliary ganglion neurons.J. Neurosci. 3, 260–271.

  75. Jacob M. H., Berg D. K., and Lindstrom J. M. (1984) Shared antigenic determinant between theElectrophorus acetylcholine receptor and a synaptic component on chicken ciliary ganglion neurons.Proc. Natl. Acad. Sci. USA 81, 3223–3227.

  76. Kalash J., Romita V., and Billiar R. B. (1989) Third ventricular injection of α-bungarotoxin decreases pulsatile luteinizing hormone secretion in the ovariectomized rat.Neuroendocrinology 49, 462–470.

  77. Karlin A. (1974) The acetylcholine receptor: a progress report.Life Sci. 14, 1385–1415.

  78. Kato E. and Narahashi T. (1982) Low sensitivity of the neuroblastoma cell cholinergic receptors to erabutoxins and α-bungarotoxin.Brain Res. 245, 159–162.

  79. Kemp G., Bentley L., McNamee M. G., and Morley B. J. (1985) Purification and characterization of the α-bungarotoxin binding protein from rat brain.Brain Res. 347, 274–283.

  80. 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. 115, 195–198.

  81. Kouvelas E. D. and Greene L. A. (1976) The binding properties and regional ontogeny of receptors for α-bungarotoxin in chick brain.Brain Res. 113, 111–126.

  82. Kouvelas E. D., Dichter M. A., and Greene L. A. (1978) Chick sympathetic neurons develop receptors for α-bungarotoxinin vitro but the toxin does not block nicotinic receptors.Brain Res. 154, 83–93.

  83. Kullberg R., Owens J. L., Camacho P., Mandel G., and Brehm P. (1990) Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed inXenopus oocytes.Proc. Natl. Acad. Sci. USA 87, 2067–2071.

  84. Kurosaki T., Fukuda K., Konno T., Mori Y., Tanaka K.-I., Mishina M., and Numa S. (1987) Functional properties of nicotinic acetylcholine receptor subunits expressed in various combinations.Fed. Eur. Biochem. Soc. 214, 253–258.

  85. Leonard J. P. and Salpeter M. M. (1982) Calcium-mediated myopathy atneuromuscular junctions of normal and dystrophic muscle.Exp. Neurology 76, 121–138.

  86. Lindstrom J., Schoepfer R., and Whiting P. (1987) Molecular studies of the neuronal nicotinic acetylcholine receptor family.Mol. Neurobiol. 1, 281–337.

  87. Lipton S. A., Aizenman E., and Loring R. H. (1987) Neural nicotinic acetylcholine responses in solitary mammalian retinal ganglion cells.Pflügers Arch. 410, 37–43.

  88. Lipton S. A., Frosch M. P., Phillips M. D., Tauck D. L., and Aizenman E. (1988) Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture.Science 239, 1293–1296.

  89. Lipton S. A. and Kater S. B. (1989) Neurotransmitter regulation of neuronal outgrowth, plasticity and survival.Trends Neurosci. 12, 265–270.

  90. Lo D. C., Pinkham J. L., and Stevens C. F. (1990) Influence of the γ subunit and expression system on acetylcholine receptor gating.Neuron 5, 857–866.

  91. Loring R. H., Chiappinelli V. A., Zigmond R. E., and Cohen J. B. (1984) Characterization of a snake venom neurotoxin which blocks nicotinic transmission in the avian ciliary ganglion.Neuroscience 11, 989–999.

  92. Loring R. H., Dahm L. M., and Zigmond R. E. (1985) Localization of α-bungarotoxin binding sites in the ciliary ganglion of the embryonic chick: an autoradiographic study at the light microscopic level.Neuroscience 14, 645–660.

  93. Loring R. H. and Zigmond R. E. (1987) Ultrastructural distribution of [125I]toxin F binding sites on chick ciliary neurons: synaptic localization of a toxin that blocks ganglionic nicotinic receptors.J. Neurosci. 7, 2153–2162.

  94. Loring R. H. and Zigmond R. E. (1988) Characterization of neuronal nicotinic receptors by snake venom neurotoxins.Trends Neurosci. 11, 73–78.

  95. Loring R. H., Aizenman E., Lipton S. A., and Zigmond R. E. (1989) Characterization of nicotinic receptors in chick retina using a snake venom neurotoxin that blocks neuronal nicotinic receptor function.J. Neurosci. 9, 2423–2431.

  96. Luetje C. W., Patrick J., and Seguela P. (1990a) Nicotine receptors in the mammalian brain.Fed. Amer. Soc. Exp. Biol. 4, 2754–2760.

  97. Luetje C. W., Wada K., Rogers S., Abramson S. N., Tsuji K., Heinemann S., and Patrick J. (1990b) Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations.J. Neurochem. 55, 632–640.

  98. Luetje C. W., and Patrick J. (1991) Both α-and β-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors.J. Neurosci. 11, 837–845.

  99. Lukas R. J., Audhya T., Goldstein G., and Lucero L. (1990) Interactions of the thymic polypeptide hormone thymopoietin with neuronal α-bungarotoxin binding sites and with muscle-type, but not ganglia-type, nicotinic acetylcholine receptor ligand-gated ion channels.Mol. Pharmacol. 38, 887–894.

  100. Marks M. J. and Collins A. C. (1982) Characterization of nicotine binding in mouse brain and comparison with the binding of α-bungarotoxin and quinuclidinylbenzilate.Mol. Pharmacol. 22, 554–564.

  101. Marks M. J., Burch J. B., and Collins A. C. (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors.J. Pharmacol. Exp. Ther. 226, 817–825.

  102. Marks M. J. and Collins A. C. (1985) Tolerance, cross-tolerance and receptors after chronic nicotine or oxotremorine.Pharmacol. Biochem. Behav. 22, 283–291.

  103. Marks M. J., Stitzel J. A., and Collins A. C. (1985) Time course study of the effects of chronic nicotine infusion on drug response and brain receptors.J. Pharmacol. Exp. Ther. 235, 619–628.

  104. Marks M. J., Stitzel J. A., Romm E., Wehner J. M., and Collins A. C. (1986a) Nicotinic binding sites in rat and mouse brain: comparison of acetylcholine, nicotine and α-bungarotoxin.Mol. Pharmacol. 30, 427–436.

  105. Marks M. J., Campbell S. M., Romm E., and Collins A. C. (1991) Genotype influences the development of tolerance to nicotine in the mouse.J. Pharmacol. Exp. Ther. 259, 392–402.

  106. Marshall L. M. (1981) Synaptic localization of α-bungarotoxin binding which blocks nicotinic transmission at frog sympathetic neurons.Proc. Nat. Acad. Sci. USA 78, 1948–1952.

  107. Matter J.-M., Matter-Sadzinski L. and Ballivet M. (1990) Expression of neuronal nicotinic acetylcholine receptor genes in the developing chick visual system.EMBO J. 9, 1021–1026.

  108. McCarthy M. P., Earnest J. P., Young E. F., Choe S., and Stroud R. M. (1986) The molecular neurobiology of the acetylcholine receptor.Ann. Rev. Neurosci. 9, 383–413.

  109. McLane K. E., Wu X., and Conti-Tronconi B. M. (1990) Identification of a brain acetylcholine receptor subunit able to bind α-bungarotoxin.J. Biol. Chem. 266, 9816–9824.

  110. McLane K. E., Wu X., Schoepfer R., Lindstrom J. M., and Conti-Tronconi B. M. (1991) Identification of sequence segments forming the α-bungarotoxin binding sites on two nicotinic acetylcholine receptor subunits from the avian brain.J. Biol. Chem. 266: 15,230–15,239.

  111. Messing A. (1982) Cholinergic agonist-induced down regulation of neuronal α-bungarotoxin receptors.Brain Res. 232, 479–484.

  112. Miledi R. and Potter L. T. (1971) A cetylcholine receptors in muscle fibers.Nature 238, 599–603.

  113. Miller M. M., Silver J., and Billiar R. B. (1982) Effects of ovariectomy on the binding of [125I]α-bungarotoxin (2.2 and 3.3) to the suprachiasmatic nucleus of the hypothalamus: an in vivo autoradiographic analysis.Brain Res. 247, 355–364.

  114. Miller M. M. and Billiar R. B. (1986a) A quantitative and morphometric evaluation of [125I]α-bungarotoxin in the rat hypothalamus.Brain Res. Bull. 16, 681–688.

  115. Miller M. M. and Billiar R. B. (1986b) Relationship of putative nicotinic cholinergic receptors in the suprachiasmatic nucleus to levels of pineal serotonin N-acetyltransferase activity in the normally cycling female, the male and the ovariectomized rat.J. Pineal Res. 3, 159–168.

  116. Miner L. L., Marks M. J., and Collins A. C. (1984) Classical genetic analysis of nicotine-induced seizures and nicotinic receptors.J. Pharmacol. Exp. Ther. 231, 545–554.

  117. Miner L. L., Marks M. J., and Collins A. C. (1986) Genetic analysis of nicotine induced seizures and hippocampal nicotinic receptors in the mouse.J. Pharmacol. Exp. Ther. 239, 853–860.

  118. Miner L. L. and Collins A. C. (1988) The effect of chronic nicotine treatment on nicotine induced seizures.Psychopharmacology 95, 52–55.

  119. 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.Nature 307, 604–608.

  120. Mishina M., Tobimatsu T., Imoto K., Tanaka K.-I., Fujita Y., Fukuda K., Kurasaki M., Takahashi H., Morimoto Y., Hirose T., Inayama S., Takahashi T., Kuno M., and Numa S. (1985) Location of functional regions of acetylcholine receptor α-subunit by site-directed mutagenesis.Nature 313, 364–369.

  121. Mishina M., Takai T., Imoto K., Noda M. Takahashi T., Numa S., Methfessel C., and Sakmann B. (1986) Molecular distinction between fetal and adult forms of muscle acetylcholine receptor.Nature 321, 406–411.

  122. Morel E., Vernet-der-Garabedian B., 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. 17, 1109–1113.

  123. Morel E., Vernet-der-Garabedian B., Raimond F., Audhya T. K., Goldstein G., and Bach J.-F. (1987) Thymopoietin: a marker of the human nicotinic acetylcholine receptor.Ann. NY Acad. Sci. 540, 298–300.

  124. Morley B. J., Kemp G. E., and Salvaterra P. (1979) α-Bungarotoxin binding sites in the CNS.Life Sci. 24, 859–872.

  125. Morley B. J. and Kemp G. E. (1981) Characterization of a putative nicotinic acetylcholine receptor in mammalian brain.Brain Res. Rev. 3, 81–104.

  126. Morley B. J., Farley G. R., and Javel E. (1983a) Nicotinic acetylcholine receptors in mammalian brain.Trends Pharmacol. Sci. 4, 225–227.

  127. Morley B. J., Rodriguez-Sierra J. F., and Clough R. W. (1983b) Increase in hypothalamic nicotinic acetylcholine receptors in prepuberal female rats administered estrogen.Brain Res. 278, 262–265.

  128. Morley B. J. and Garner L. L. (1990) Light-dark variation in response to chronic nicotine treatment and the density of hypothalamic α-bungarotoxin receptors.Pharmacol. Biochem. Behav. 37, 239–245.

  129. Mulle C. and Changeux J.-P. (1990) A novel type of nicotinic receptor in the rat central nervous system characterized by patch-clamp techniques.J. Neurosci. 10, 169–175.

  130. Mulle C., Vidal C., Benoit P., and Changeux J.-P. (1991) Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system.J. Neurosci. 11, 2588–2597.

  131. Nef P., Oneyser C., Alliod C., Couturier S., Ballivet M. (1988) Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors.EMBO J. 7, 595–601.

  132. Noda M., Takahashi H., Tanabe T., Toyosato M., Furutani Y., Hirose T., Asai M., Inayama S., Miyata T., and Numa S. (1982) Primary structure of α-subunit precursor ofTorpedo californica acetylcholine receptor deduced from cDNA sequence.Nature 298, 793–797.

  133. 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.Nature 302, 528–532.

  134. Norman R. I., Mehraban F., Barnard E. A., and Dolly J. O. (1982) Nicotinic acetylcholine receptor from chick optic lobe.Proc. Nat. Acad. Sci. USA 79, 1321–1325.

  135. 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. 8, 325–331.

  136. Ochoa E. L. M., Chattopadhyay A., and McNamee M. G. (1989) Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators.Cell. Mol. Neurobiol. 9, 141–178.

  137. Ochoa E. L. M., Li L., Plummer A., and McNammee M. G. (1990) Direct effects of thymopentin (arg-lysasp-val-tyr) on cholinergic agonist-induced slow inactivation of nicotinic acetylcholine receptor function.Mol. Pharmacol. 38, 863–871.

  138. Oswald R. E. and Freeman J. A. (1981) Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors.Neuroscience 6, 1–14.

  139. Papke R. L. and Heinemann S. F. (1991) The role of the β4 subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine α3 receptors.J. Physiol. 440, 95–112.

  140. Patrick J. and Stallcup W. B. (1977a) Immunological distinction between acetylcholine receptor and the α-bungarotoxin-binding component on sympathetic neurons.Proc. Nat. Acad. Sci. USA 74, 4689–4692.

  141. Patrick J. and Stallcup B. (1977b) α-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line.J. Biol. Chem. 252, 8629–8633.

  142. Pauly J. R. and Horseman N. D. (1988a) Autoradiographic localization of bungarotoxin binding sites in the suprachiasmatic region of rat brain.Brain Res. 452, 105–112.

  143. Pauly J. R. and Horseman N. D. (1988b) Perturbations of locomotor activity rhythms following suprachiasmatic bungarotoxin infusion.Physiol. Behav. 43, 859–865.

  144. Pauly J. R., Grun E. U., and Collins A. C. (1990a) The effects of chronic corticosterone administration on sensitivity to nicotine and nicotinic cholinergic receptor binding are reversible.Neurosci. Abstr. 16, 204.

  145. Pauly J. R., Ullman E. A., and Collins A. C. (1990b) Strain differences in adrenalectomy-induced alterations in nicotine sensitivity in the mouse.Pharmacol. Biochem. Behav. 35, 171–179.

  146. Pauly J. R., Marks M. J., Gross S. D., and Collins A. C. (1991) An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment.J. Pharmacol. Exp. Ther. 258, 1127–1136.

  147. Quik M. and Lamarca M. V. (1982) Blockade of transmission in rat sympathetic ganglia by a toxin which co-purifies with α-bungarotoxin.Brain Res. 238, 385–399.

  148. Quik M. and Trifaró J.-M. (1982) The α-bungarotoxin site and its relation to the cholinergic and nerve growth factor mediated increase in tyrosine hydroxylase activity in cultures of sympathetic ganglia and chromaffin cells.Brain Res. 244, 331–336.

  149. Quik M., Geertsen S., and Trifaró J.-M. (1987) Marked up-regulation of the α-bungarotoxin site in adrenal chromaffin cells by specific nicotinic antagonists.Mol. Pharmacol. 31, 385–391.

  150. Quik M. and Geertsen S. (1988) Neuronal nicotinic α-bungarotoxin sites.Can. J. Physiol. Pharmacol. 66, 971–979.

  151. Quik M., Afar R., Audhya T., and Goldstein G. (1989) Thymopoietin, a thymic polypeptide, specifically interacts at neuronal nicotinic α-bungarotoxin receptors.J. Neurochem. 53, 1320–1323.

  152. Quik M., Afar R., Geertsen S., Audhya T., Goldstein G., and Trifaro J.-M. (1990a) Thymopietin, a thymic polypeptide, regulates nicotinic α-bungarotoxin sites in chromaffin cells in culture.Mol. Pharmacol. 37, 90–97.

  153. Quik M., Cohen R., Audhya T., and Goldstein G. (1990b) Thymopoietin interacts at the α-bungarotoxin site of and induces process formation in PC12 pheochromocytoma cells.Neuroscience 39, 139–150.

  154. Quik M., Collier B., Audhya T., and Goldstein G. (1990c) Thymopoietin inhibits function and ligand binding to nicotinic receptors at the neuromuscular junction.J. Pharmacol. Exp. Ther. 254, 1113–1119.

  155. Quik M., Babu U., Audhya T., and Goldstein G. (1991a) Evidence for thymopoietin and thymopoietin/ α-bungarotoxin/nicotinic receptors within the brain.Proc. Nat. Acad. Sci. USA 88, 2603–2607.

  156. Quik M., El-Bizri H., Audhya T., and Goldstein G. (1991b) Thymopoietin, a potent antagonist at nicotinic receptors in C2 muscle cell cultures.Mol. Pharmacol. 39, 324–331.

  157. Quik M., Philie J., and Goldstein G. (1992) Thymopoietin a thymic polypeptide, prevents nicotinic agonist induced degeneration in neonatal muscle cells in culture.Neuroscience, submitted.

  158. Ravdin P. M. and Berg D. K. (1979) Inhibition of neuronal acetylcholine sensitivity by α-toxins fromBungarus multicinctus venom.Proc. Natl. Acad. Sci. USA 76, 2072–2076.

  159. 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. USA 84, 3477–3481.

  160. Sah D. W. Y., Loring R. H., and Zigmond R. E. (1987) Long-term blockade by toxin F of nicotinic synaptic potentials in cultured sympathetic neurons.Neuroscience 3, 867–874.

  161. Saiani L., Kageyama H., Conti-Tronconi B. M., and Guidotti A. (1984) Purification and characterization of a bungarotoxin polypeptide which blocks nicotinic receptor function in primary culture of adrenal chromaffin cells.Mol. Pharmacol. 25, 327–334.

  162. Sakmann B., Methfessel C., Mishina M., Takahashi T., Takai T., Kurasaki M., Fukuda K., and Numa S. (1985) Role of acetylcholine receptor subunits in gating of the channel.Nature 318, 538–543.

  163. Salpeter M. M. and Loring R. H. (1985) Nicotinic acetylcholine receptors in vertebrate muscle: properties, distribution, and neural control.Prog. Neurobiol. 25, 297–325.

  164. Schaffner A. E. and Olek A. J. (1986) The developmental appearance of α-bungarotoxin binding sites on rodent spinal cord neurons in cell culture.Dev. Brain Res. 25, 239–247.

  165. Scheid M. P., Goldstein G., and Boyse E. A. (1978) The generation and regulation of lymphocyte populations: evidence from differentiative induction systemsin vitro.J. Exp. Med. 147, 1727–1743.

  166. Schmidt J. (1977) Drug binding properties of an α-bungarotoxin binding component from rat brain.Mol. Pharmacol. 13, 283–290.

  167. Schoepfer R., Conroy W. G., Whiting P., Gore M., and Lindstrom J. (1990) Brain α-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily.Neuron 5, 35–48.

  168. Schulz D. H., Loring R. H., Aizenman E., and Zigmond R. E. (1991) Autoradiographic localization of putative nicotinic receptors in the rat brain using [125I] neuronal bungarotoxin.J. Neurosci. 11, 287–297.

  169. Schwartz R. D., McGee R., and Kellar K. J. (1982) Nicotinic cholinergic receptors labeled by [3H] acetylcholine in rat brain.Mol. Pharmacol. 22, 55–62.

  170. Smolen A. J. (1983) Specific binding of α-bungarotoxin to synaptic membranes in rat sympathetic ganglion: computer best-fit analysis of electron microscope radioautographs.Brain Res. 289, 177–188.

  171. Steinbach J. H. (1989) Structural and functional diversity in vertebrate skeletal muscle nicotinic acetylcholine receptors.Ann. Rev. Physiol. 51, 353–365.

  172. Steinbach J. H. and Ifune C. (1989) How many kinds of nicotinic acetylcholine receptors are there?Trends Neurosci. 12, 3–6.

  173. Stevens C. F. (1985) AChR structure: a new twist in the story.Trends Neurosci. 8, 1,2.

  174. Stroud R. M., McCarthy M. P., and Shuster M. (1990) Nicotinic acetylcholine receptor superfamily of ligand gated ion channels.Biochemistry 29, 11,009–11,023.

  175. Sunshine G. H., Basch R. S., Coffey R. G., Cohen K. W., Goldstein G., and Hadden J. W. (1978) Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes.J. Immunol. 120, 1594–1599.

  176. Swanson L. W., Lindstrom J., Tzartos S., Schmued L. C., O'Leary D. M., and Cowan W. M. (1983) Immunohistochemical localization of monoclonal antibodies to the nicotinic acetylcholine receptor in chick midbrain.Proc. Natl. Acad. Sci. USA 80, 4532–4536.

  177. Swanson L. W., Simmons D. M., Whiting P. J., and Lindstrom J. (1987) Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system.J. Neurosci. 7, 3334–3342.

  178. Syapin P. J., Salvaterra P. M., and Engelhardt J. K. (1982) Neuronal-like features of TE671 cells: presence of a functional nicotinic cholinergic receptor.Brain Res. 231, 365–377.

  179. Takai T., Noda M., Mishina M., Shimizu S., Furutani Y., Kayano T., Ikeda T., Kubo T., Takahashi H., Takahashi T., Kuno M., and Numa S. (1985) Cloning sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle.Nature 315, 761–764.

  180. Twomey J. J., Goldstein G., Lewis V. M., Bealmear P. M., and Good R. A. (1977) Bioassay determinations of thymopoietin and thymic hormone levels in human plasma.Proc. Natl. Acad. Sci. USA 74, 2541–2545.

  181. Venkatasubramanian K., Audhya T., and Goldstein G. (1986) Binding of thymopoietin to the acetylcholine receptor.Proc. Natl. Acad. Sci. USA 83, 3171–3174.

  182. Vidal C. and Changeux J.-P. (1989) Pharmacological profile of nicotinic acetylcholine receptors in the rat prefrontal cortex: an electrophysiological study in a slice preparation.Neuroscience 29, 261–270.

  183. Vogel Z. and Nirenberg M. (1976) Localization of acetylcholine receptors during synaptogenesis in retina.Proc. Natl. Acad. Sci. USA 73, 1806–1810.

  184. Wada E., Wada K., Boulter J., Deneris E., Heinemann S., Patrick J., and Swanson L. W. (1989) Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat.J. Comp. Neurol. 284, 314–335.

  185. Wada K., Ballivet M., Boulter J., Connolly J., Wada E., Deneris E. S., Swanson L. W., Heinemann S., and Patrick J. (1988) Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor.Science 240, 330–334.

  186. Wade P. D. and Timiras P. S. (1980) Whole brain and regional [125I]-bungarotoxin binding in developing rat.Brain Res. 181, 381–389.

  187. Wan K. K. and Lindstrom J. (1984) Nicotinic acetylcholine receptor.The Receptors I, 377–430.

  188. Whiting P. and Lindstrom J. (1986) Pharmacological properties of immuno-isolated neuronal nicotinic receptors.J. Neurosci. 6, 3061–3069.

  189. Whiting P. and Lindstrom J. (1987) Purification and characterization of a nicotinic acetylcholine receptor from rat brain.Proc. Natl. Acad. Sci. USA 84, 595–599.

  190. Whiting P., Liu R., Morley B. J., and Lindstrom J. (1987a) Structurally different neuronal nicotinic acetylcholine receptor subtypes purified and characterized using monoclonal antibodies.J. Neurosci. 7, 4005–4016.

  191. Whiting P. J., Schoepfer R., Swanson L. W., Simmons D. M., and Lindstrom J. M. (1987b) Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptors.Nature 327, 515–518.

  192. Witzemann V., Barg B., Nishikawa Y., Sakmann B., and Numa S. (1987) Differential regulation of muscle acetylcholine receptor γ- and ε-subunit mRNAs.Fed. Eur. Biochem. Soc. 223, 104–112.

  193. Witzemann V., Stein E., Barg B., Konno T., Koenen M., Kues W., Criado M., Hofmann M., and Sakmann B. (1990) Primary structure and functional expression of the α-, β-, γ-, δ- and ε-subunits of the acetylcholine receptor from rat muscle.Eur. J. Biochem. 194, 437–448.

  194. Wong L. A. and Gallagher J. P. (1989) A direct nicotinic receptor-mediated inhibition recorded intracellularlyin vitro.Nature 341, 439–442.

  195. Wong L. A. and Gallagher J. P. (1991) Pharmacology of nicotinic receptor-mediated inhibition in rat dorsolateral septal neurones.J. Physiol. (Lond) 436, 325–346.

  196. Zatz M. and Brownstein M. J. (1981) Injection of α-bungarotoxin near the suprachiasmatic nucleus blocks the effects of light on nocturnal pineal enzyme activity.Brain Res. 213, 438–442.

  197. Zhang Z. W. and Feltz P. (1990) Nicotinic acetylcholine receptors in porcine hypophyseal intermediate lobe cells.J. Physiol. (Lond) 422, 83–101.

Download references

Author information

Correspondence to Maryka Quik.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Quik, M. Thymopoietin, a thymic polypeptide, potently interacts at muscle and neuronal nicotinic α-bungarotoxin receptors. Mol Neurobiol 6, 19–40 (1992). https://doi.org/10.1007/BF02935565

Download citation

Index Entries

  • Nicotinic receptors
  • α-bungarotoxin
  • ACh
  • thymopoietin
  • nicotine