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Nicotinic acetylcholine receptors in health and disease

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Abstract

Nicotinic acetylcholine receptors (AChRs) are a family of acetylcholine-gated cation channels that form the predominant excitatory neurotransmitter receptors on muscles and nerves in the peripheral nervous system. AChRs are also expressed on neurons in lower amounts throughout the central nervous system. AChRs are even being reported on unexpected cell types such as keratinocytes. Structures of these AChRs are being determined with increasing precision, but functions of some orphan subunits are just beginning to be established. Functional roles for postsynaptic AChRs in muscle are well known, but in neurons the post-, peri-, extra-, and presynaptic roles of AChRs are just being revealed. Pathogenic roles of AChRs are being discovered in many diseases involving mechanisms ranging from mutations, to autoimmune responses, to the unknown; involving cell types ranging from muscles, to neurons, to keratinocytes; and involving signs and symptoms ranging from muscle weakness to epilepsy, to neurodegenerative disease, to psychiatric disease, to nicotine addiction. Awareness of AChR involvement in some of these diseases has provoked new interests in development of therapeutic agonists for specific AChR subtypes and the use of expressed cloned AChR subunits as possible immunotherapeutic agents. Highlights of recent developments in these areas will be briefly reviewed.

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References

  • Akaike A., Tamura Y., Yokota T., Shimohama S., and Kimura J. (1994) Nicotine-induced protection of cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.Brain Res. 644, 181–187.

    Article  PubMed  CAS  Google Scholar 

  • Albuquerque E., Alkondon M., Pereira E., Castro N., Schrattenholz A., Barbosa C., Bonfante-Cabarcas R., Aracava Y., Eisenberg H., and Melicke A. (1996) Properties of neuronal nicotinic acetylcholine receptors, pharmacological characterization and modulation of synaptic function.J. Pharmacol. Exp. Ther. 280, 1117–1136.

    Google Scholar 

  • Akabas M. and Karlin A. (1995) Identification of acetylcholine receptor channel-lining residues in the M1 segment of the a subunit.Biochemistry 34, 12,596–12,500.

    Article  Google Scholar 

  • Akabas M., Kaufmann C., Archdeacon P., and Karlin A. (1994) Identification of acetylcholine receptor channel-liming residues in the entire M2 segment of the a subunit.Neuron 13, 919–927.

    Article  PubMed  CAS  Google Scholar 

  • Akabas M., Stauffer D., Xu M., and Karlin A. (1992) Acetylcholine receptor channel structure probed in cysteine-substitution mutants.Science 258, 307–310.

    Article  PubMed  CAS  Google Scholar 

  • Anand R., Conroy W., Schoepfer R., Whiting P., and Lindstrom J. (1991) Chicken neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure.J. Biol. Chem. 266, 11,191–11,198.

    Google Scholar 

  • Anand R., Peng X., Ballesta J., and Lindstrom J. (1993) Pharmacological characterization of αbungarotoxin sensitive AChRs immunoisolated from chick retina, contrasting properties of α7 and α8 subunit-containing subtypes.Mol. Pharmacol. 44, 1046–1050.

    PubMed  CAS  Google Scholar 

  • Arcavi L., Jacob P., Hellerstein M., and Benowitz N. (1994) Divergent tolerance to metabolic and cardiovascular effects of nicotine in smokers with low and high levels of cigarette consumption.Clin. Pharmacol. Ther. 56, 55–64.

    Article  PubMed  CAS  Google Scholar 

  • Arneric S., Sullivan J., Briggs C., Donnelly-Roberts D., Anderson D., Roszkiewicz J., Hughes M., Cadman E., Adams P., Garvey D., Wasicak J., and Williams M. (1994) (S)-3methyl-5(1-methyl-2pyrrolidinyl) isoxazole (ABT418), a novel cholinergic ligand with cognition-enhancing and anxiolytic activities, 1. in vitro characterization.J. Pharmacol. Exper. Ther. 270, 310–318.

    CAS  Google Scholar 

  • Arnold A. and Trojanowski J. (1996) Recent advances in defining the neuropathy of schizophrenia.Acta Neuropathol. 92, 217–231.

    Article  PubMed  CAS  Google Scholar 

  • Barnard E. (1992) Receptor classes and the transmitter-gated ion channels.TIBS 17, 368–374.

    PubMed  CAS  Google Scholar 

  • Benowitz N. (1996) Pharmacology of nicotine, addiction and therapeutics.Annu. Rev. Pharmacol. Toxicol. 36, 597–613.

    Article  PubMed  CAS  Google Scholar 

  • Benowitz N., Prochet H., and Jacob P. (1990) Pharmacokinetics, metabolism, and pharmacodynamics of nicotine, inNicotine Psychopharmacology (Wonnocott S., Russell M., and Stolerman I., eds.), Oxford Science Publication, Oxford England, pp. 112–157.

    Google Scholar 

  • Benwell M., Balfour D., and Anderson J. (1988) Evidence that tobacco smoking increases the density of (−)-3H] nicotine binding sites in human brain.J. Neurochem. 50, 1243–1247.

    Article  PubMed  CAS  Google Scholar 

  • Beroukhim R. and Unwin N. (1995) Three dimensional location of the main immunogenic region of the acetylcholine receptor.Neuron 15, 323–331.

    Article  PubMed  CAS  Google Scholar 

  • Bertrand S., Buisson B., Forster I., and Bertrand D. (1995) Determinnants regulating neuronal nicotinic receptor function, inEffects of Nicotine on Biological Systems II, Advances in Pharmacological Sciences (Clarke P., Quik M., Adlkofer F., and Thurau K., eds.), Birkhauser, Basel, pp. 53–59.

    Google Scholar 

  • Betz H. (1990) Homology and analogy in transmembrane channel design, lessons from synaptic membrane proteins.Biochemistry 29, 3591–3599.

    Article  PubMed  CAS  Google Scholar 

  • Bickford P. and Wear K. (1995) Restoration of sensory gating of auditory evoked response by nicotine in fimbria-fornix lesioned rats.Brain Res. 705, 235–240.

    Article  PubMed  CAS  Google Scholar 

  • Birtwiselle J. (1996) The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.Postgrad Med. J. 72, 714–718.

    Google Scholar 

  • Bjugastad K., Mahnir V., Kein W., Socci D., and Arendash G. (1996) Long term treatment with GTS-21 or nicotine enhances water maze performance in aged rats without affecting the density of nicotinic receptor subtypes in neocortex.Drug Develop. Res. 39, 19–28.

    Article  Google Scholar 

  • Blomquist O., Engel J., Bissbrandt H., and Soderpalm B. (1993) The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine.Eur. J. Pharmacol. 249, 207–213.

    Article  Google Scholar 

  • Blount P. and Merlie J. (1989) Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor.Neuron 3, 349–357.

    Article  PubMed  CAS  Google Scholar 

  • Chan J. and Quik M. (1993) A role for the nicotinic αbungarotoxin receptor in neurite outgrowth in PC12 cells.Neuroscience 56, 441–451.

    Article  PubMed  CAS  Google Scholar 

  • Changeux J. (1990) Functional architecture and dynamics of the nicotinic acetylcholine receptor, an allosteric ligand-gated ion channel, inFidia Research Foundation, Neuroscience Award Lectures, vol. 4, 21–168

  • Clarke P., Schwartz R., Paul S., Pert C., and Pert A. (1985) Nicotinic binding in rat brain, autoradiographic comparison of [3H] acetylcholine, [3H] nicotine, and [125I] αbungarotoxin.J. Neurosci. 5, 1307–1315.

    PubMed  CAS  Google Scholar 

  • Codignola A., Tarroni P., Cattaneo M., Vincentini L., Clementi F., and Sher E. (1994) Serotonin release and cell proliferation are under control of αbungarotoxin-sensitive nicotinic receptors in small-cell lung carcinoma cell lines.FEBS Lett. 342, 286–290.

    Article  PubMed  CAS  Google Scholar 

  • Coleman R. (1992) Current drug therapy for Parkinson's disease. A review.Drugs Aging 2, 112–124.

    PubMed  CAS  Google Scholar 

  • Collins A., Burch J., DeFiebre C., and Marks M. (1987) Tolerance and cross tolerance between ethanol and nicotine.Pharmacol. Biochem. Behavior 29, 365–373.

    Article  Google Scholar 

  • Collins A. and Marks M. (1996) Are nicotinic receptors activated or inhibited following chronic nicotine treatment?Drug. Develop. Res. 38, 231–242.

    Article  CAS  Google Scholar 

  • Conroy W. and Berg D. (1995) Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions.J. Biol. Chem. 270, 4424–4431.

    Article  PubMed  CAS  Google Scholar 

  • Conroy W., Vernallis A., and Berg D. (1992) The α gene product assembles with multiple acetylcholine receptor subunits to form, distinctive receptor subtypes in brain.Neuron 9, 1–20.

    Article  Google Scholar 

  • Conti-Tronconi B., Tzartos S., and Lindstrom J. (1981) Monoclonal antibodies as probes of acetylcholine receptor structure. II, Binding to native receptor.Biochemistry 20, 2181–2191.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Croxen R., Newland C., Beeson D., Oosterhuis H, Chauplannaz G., Vincent A., and Newsome-Davis J. (1997) Mutations in different functional domains of the human muscle acetylcholine receptor α subunit in patients with the slow channel congenital myasthenic syndrome.Human Mol. Genetics 6, 767–774.

    Article  CAS  Google Scholar 

  • Czajkowski C. and Karlin A. (1995) Structure of the nicotinic receptor acetylcholine binding site.J. Biol. Chem. 270, 3160–3164.

    Article  PubMed  CAS  Google Scholar 

  • Czajkowski C., Kaufmann C., and Karlin A. (1993) Negatively charged amino acid residues in the nicotinic receptor α subunit that contribute to the binding of acetylcholine.Proc. Natl. Acad. Sci. USA 90, 6294–6289.

    Article  Google Scholar 

  • Dani J and Heinemann S. (1996) Molecular and cellular aspects of nicotine abuse.Neuron 16, 905–908.

    Article  PubMed  CAS  Google Scholar 

  • Decker M., Brioni J., Sullivan J., Buckley M., Rodek R., Rasziewicz J., Kang, C., Kim D., Giardina W., Wasicak J., Garvey D., Williams M., and Arneric S. (1994) (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxasole (ABT418), a novel cholinergic ligand with cognition-enhancing and anxiolytic activities, II. in vitro characterization.J. Pharmacol. Exper. Ther. 270, 319–328.

    CAS  Google Scholar 

  • Deitrich R., Dunwiddie T., Harris R., and Erwin V. (1989) Mechanism of action of ethanol, initial central nervous system actions.Pharmacol. Rev. 41, 489–537.

    PubMed  CAS  Google Scholar 

  • Del Toro E., Juiz J., Peng X., Lindstrom J., and Criado M. (1994) Immunocytochemical localization of the a7 subunit of the nicotinic acetylcholine receptor in the rat central nervous system.J. Comp. Neurol. 349, 325–342.

    Article  Google Scholar 

  • Dichter M. (1994) Epilepsy, inBiological Basis of Brain Function and Disease (Frazer A., Molinoff P., and Winokur A., eds.), Raven, New York, pp. 406–423.

    Google Scholar 

  • Donnelly-Roberts D., Xue J., Arneric S., and Sullivan J. (1996) In vitro neuroprotective activator (ChCA) ABT-418.Brain Res. 719, 36–44.

    Article  PubMed  CAS  Google Scholar 

  • Drachman D. (1994) Myasthenia gravis.N. Engl. J. Med. 330, 1797–1810.

    Article  PubMed  CAS  Google Scholar 

  • Drachman D., Okumura S., Adams R., and McIntosh K. (1996) Oral tolerance in myasthenia gravis.Ann. NY Acad. Sci 778, 258–272.

    Article  PubMed  CAS  Google Scholar 

  • Dursun S., Reveley M., Bird R., and Stirton F. (1992) Long lasting improvement of Tourette's syndrome with transdermal nicotine.Lancet 344, 1577.

    Article  Google Scholar 

  • Eisile J., Bertrand S., Galzi J., Devillers-Thiery A., Changeux J., and Bertrand D. (1993) Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities.Nature 366, 479–483.

    Article  Google Scholar 

  • Elgoyhen A., Johnson D., Boulter J., Vetter D., and Heinemann S. (1994) α9, An acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.Cell 79, 705–715.

    Article  PubMed  CAS  Google Scholar 

  • Engel A. (1994) The neuromuscular junction, inMyology 2nd ed., vol. 1 (Engel A. and Franzini-Armstrong C., eds.), McGraw Hill, New York, pp. 261–302.

    Google Scholar 

  • Engel A., Hutchinson D., Nakano S., Murphy L., Griggs R., Gu Y., Hall Z., and Lindstrom J. (1993a) Myasthenic syndromes attributed to mutations affecting the ε subunit of the acetylcholine receptor.Ann. NY Acad. Sci. 681, 496–508.

    Article  PubMed  CAS  Google Scholar 

  • Engel A., Uchitel O., Walls T., Nagel A., Harper C., and Bodensteiner J. (1993b) Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel.Ann. Neurol. 34, 38–47.

    Article  PubMed  CAS  Google Scholar 

  • Engel A., Ohno K., Bouzat C., Sine S., and Griggs R. (1996a) End plate acetylcholine receptor deficiency due to nonsense mutations in the ε subunit.Ann. Neurol. 40, 810–817.

    Article  PubMed  CAS  Google Scholar 

  • Engel A., Ohno K., Milone M., Wang H., Nakano S., Bouzat C., Pruitt J., Hutchinson D., Brengman J., Bren N., Sieb J., and Sine S. (1996b) New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow channel congenital myasthenic syndrome.Human Mol. Genetics 5, 1217–1227.

    Article  CAS  Google Scholar 

  • Engel A., Ohno K., Milone M., and Sine S. (1997) Congenital myasthenic syndromes caused by mutations in acetylcholine receptor genes.Neurology 48 (Suppl. 5), S28-S35.

    CAS  Google Scholar 

  • Everitt B. and Robbins T. (1997) Central cholinergic systems and cognition.Annu. Rev. Psychol. 48, 649–684.

    Article  PubMed  CAS  Google Scholar 

  • Evers A. and Steinbach J. (1997) Supersensitive sites in the central nervous system.Anesthesiology 86, 760–762.

    Article  PubMed  CAS  Google Scholar 

  • Flood P., Ramirez-Latorre J., and Role L. (1997) α4β2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but α7-type nicotinic acetylcholine receptors are unaffected.Anesthesiology 86, 859–865.

    Article  PubMed  CAS  Google Scholar 

  • Flores C., Rogers S., Pabreza L., Wolfe B., and Kellar K. (1992) A subtype of nicotinic cholinergic receptor in rat brain is composed of α4 and β2 subunits and is upregulated by chronic nicotine treatment.Mol. Pharmacol. 41, 31–37.

    PubMed  CAS  Google Scholar 

  • Forsayeth J. and Kobrin E. (1997) Formation of oligomers containing the β3 and β4 subunits of the rat nicotinic receptor.J. Neurosci. 17, 1531–1538.

    PubMed  CAS  Google Scholar 

  • Franks N. and Lieb W. (1994) Molecular and cellular mechanisms of general anesthesia.Nature 367, 607–614.

    Article  PubMed  CAS  Google Scholar 

  • Freedman R., Coon H., Myles-Worsley M., Orr-Urtreger A., and Olincey A. (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.Proc. Natl. Acad. Sci. USA 94, 587–592.

    Article  PubMed  CAS  Google Scholar 

  • Freedman R., Hall M., Adler L., and Leonard S. (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia.Biopsychology 38, 22–33.

    CAS  Google Scholar 

  • Fu D. and Sine S. (1994) Competitive antagonists bridge α-γ subunit interface of the acetylcholine receptor through quaternary aromatic interactions.J. Biol. Chem. 269, 26,152–26,157.

    CAS  Google Scholar 

  • Fu D. and Sine S. (1996) Asymmetric contribution to the conserved disulfide loop to subunit oligomerization and assembly of the nicotinic acetylcholine receptor.J. Biol. Chem. 271, 31,479–31,484.

    Article  CAS  Google Scholar 

  • Fuchs P. (1996) Synaptic transmission at vertebrate hair cells.Curr. Opin. Neurobiol. 6, 514–519.

    Article  PubMed  CAS  Google Scholar 

  • Fucile S., Napolitano M., and Mattei E. (1997) Cholinergic stimulation of human microcitoma cell line H69.Biochem. Biophys. Res. Commun. 230, 501–504.

    Article  PubMed  CAS  Google Scholar 

  • Furness J. and Costa M. (1987)The Enteric Nervous System. Churchill Livingstone, New York.

    Google Scholar 

  • Galzi V. and Changeux V. (1994) Neurotransmittergated ion channels as unconventional allosteric proteins.Curr. Opin. Struct. Biol. 4, 554–565.

    Article  CAS  Google Scholar 

  • Galzi J., Bertrand D., Devillers-Thiery A., Revah F., Bertrand S., and Changeux J. (1991) Functional significance of aromatic amino acids from three peptide loops of the α7 neuronal nicotinic receptor site investigated by site directed mutagenesis.FEBS Lett. 294, 198–202.

    Article  PubMed  CAS  Google Scholar 

  • Galzi J., Devillers-Thiery A., Hussy N., Bertrand S., Changeux J., and Bertrand D. (1992) Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.Nature 359, 500–505.

    Article  PubMed  CAS  Google Scholar 

  • Galzi J., Revah F., Black D., Goeldner M., Hirth C., and Changeux J. (1990) Identification of a novel amino acid alpha tyrosine 93 within the cholinergic ligand-binding sites of the acetylcholine receptor by photoaffinity labeling.J. Biol. Chem. 265, 10,430–10,437.

    CAS  Google Scholar 

  • Galzi J., Revah F., Bouet F., Menez A., Coeldner M., Hirth C., and Changeux J. (1991) Allosteric transitions of the acetylcholine receptor probed at the amino acid level with a photolabile cholinergic ligand.Proc. Natl. Acad. Sci. USA 88, 5051–5055.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Guzman M., Sala F., Sala S., Campos-Caro A., Stuhmer W., Gutierrez L., and Criado M. (1995) αbungarotoxin-sensitive nicotinic receptors on bovine chromaffin cells, molecular cloning, functional expression and alternative splicing of the α7 subunit.Eur. J. Neurosci. 7, 647–655.

    Article  PubMed  CAS  Google Scholar 

  • Gattenlohner S., Brabletz T., Schultz A., Marx A., Muller-Hermelink H., and Kirchner T. (1994) Cloning of a cDNA coding for the acetylcholine receptor α subunit from a thymoma associated with myasthenia gravis.Thymus 23, 103–113.

    PubMed  CAS  Google Scholar 

  • Gerzanich V., Anand R., and Lindstrom J. (1994) Homomers of α8 subunits of nicotinic receptors functionally expressed inXenopus oocytes exhibit similar channel but contrasting binding site properties compared to α7 homomers.Mol. Pharmacol. 45, 212–220.

    PubMed  CAS  Google Scholar 

  • Gerzanich V., Kuryatov A., Anand R., and Lindstrom J. (1997) “Orphan” α6 nicotinic AChR subunit can form a functional heteromeric acetylcholine receptor.Mol. Pharmacol. 51, 320–327.

    PubMed  CAS  Google Scholar 

  • Gomez C., Bhattacharyya B., Charnet P., Day J., Labarca C., Wollmann R., and Lambert E. (1996) A transgenic mouse model of the slow-channel syndrome.Muscle and Nerve 19, 79–87.

    Article  PubMed  CAS  Google Scholar 

  • Gomez C. and Gammack J. (1995) A leucine to phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow channel syndrome.Neurology 45, 982–985.

    PubMed  CAS  Google Scholar 

  • Gomez C., Maselli R., Gammack J., Lasalde J., Tamamizu S., Cornblath D., Lehar M., McNamee M., and Kuncl R. (1996) A β subunit mutation in the acetylcholine receptor channel gate causes severe slow channel syndrome.Ann. Neurol. 39, 712–723.

    Article  PubMed  CAS  Google Scholar 

  • Gopalakrishnan M., Buison B., Touma E., Giordano T., Campbell J., Hu J., Donnelly-Roberts D., Arneric S., Bertrand D., and Sullivan J. (1995) Stable expression and pharmacological properties of the human α7 nicotinic acetylcholine receptor.Eur. J. Pharmacol. 290, 237–246.

    Article  PubMed  CAS  Google Scholar 

  • Gopalakrishnan M., Monteggia L., Anderson D., Molinari E., Piattoni-Kaplan M., Donnelly-Roberts D., Arneric S., and Sullivan J. (1996) Stable expression, pharmacologic properties and regulation of the human neuronal nicotinic acetylcholine α4β2 receptor.J. Pharmacol. Exp. Ther. 276, 289–297.

    PubMed  CAS  Google Scholar 

  • Gotti C., Briscini L., Vergerio C., Oortgiesen M., Balestra B., and Clementi F. (1995) Native nicotinic acetylcholine receptors in human Imr32 neuroblastoma cells, functional, immunological, and pharmacological properties.Eur. J. Neurosci. 7, 2083–2092.

    Article  PubMed  CAS  Google Scholar 

  • Grando S., Horton R., Pereira E., Diethelmokita B., George P., Albuquerque E., and Contifine B. (1995) A nicotinic acetylcholine receptor regulating cell adhesion and motility is expressed in human keratinocytes.J. Invest. Dermatol. 105, 774–781.

    Article  PubMed  CAS  Google Scholar 

  • Grando S., Horton R., Mauro T., Kist D., Lee T., and Dahl M. (1996) Activation of keratinocyte nicotinic cholinergic receptors stimulates calcium influx and enhances cell differentiation.J. Invest. Dermatol. 107, 412–418.

    Article  PubMed  CAS  Google Scholar 

  • Gray R., Rajan A., Radcliffe K., Yakehiro M., and Dani J. (1996) Hippocampal synaptic transmission enhanced by low concentrations of nicotine.Nature 383, 713–716.

    Article  PubMed  CAS  Google Scholar 

  • Green J., Thomas G., Rhodes J., Evans B., Russell M., Feyerabend C., Fuller G., Newcombe R., and Sandborn W. (1997) Pharmacokinetics of nicotine carbomer enemas, a new treatment for ulcerative colitis.Clin. Pharmacol. Ther. 61, 340–348.

    Article  PubMed  CAS  Google Scholar 

  • Guslandi M. and Tittpbello A. (1996) Pilot trial of nicotine patches as an alternative to corticosteroids.J. Gastroenterol. 31, 627–629.

    Article  PubMed  CAS  Google Scholar 

  • Hara H., Hayashi K., Ohta K., Itoh N., and Ohta M. (1993) Nicotinic acetylcholine receptor mRNAs in myasthenic thymuses.Biochem. Biophys. Res. Commun. 194, 1269–1275.

    Article  PubMed  CAS  Google Scholar 

  • Henningfield J. (1984) Behavioral pharmacology of smoking, inAdvances in Behavioral Pharmacology, vol. 4 (Thompson T., Deros P., and Barrett J., eds.), Academic, Orlando, FL, pp. 131–210.

    Google Scholar 

  • Henningfield J., Chail L., and Griffith R. (1984) Effects of ethanol on cigarette smoking by volunteers without histories of alcoholism.Psychopharmacology 82, 1–5.

    Article  PubMed  CAS  Google Scholar 

  • Hardy J. (1997) The Alzheimer family of diseases, many etiologies, one pathogenesis?Proc. Natl. Acad. Sci. USA 94, 2095–2097.

    Article  PubMed  CAS  Google Scholar 

  • Horch H. and Sargent P. (1995) Perisynaptic surface distribution of multiple classes of nicotinic acetylcholine receptors on neurons in the chicken ganglion.J. Neurosci. 15, 7778–7795.

    PubMed  CAS  Google Scholar 

  • Horch H. and Sargent P. (1996) Synaptic and extrasynaptic distribution of two distinct populations of nicotinic acetylcholine receptor clusters in the frog cardiac ganglion.J. Neurocytol. 25, 67–77.

    Article  Google Scholar 

  • Hsu Y., Amin J., Weiss D., and Wecker L. (1996) Sustained nicotine exposure differentially affects α3β2 and α4β2 neuronal nicotinic receptors expressed inXenopus oocytes.J. Neurochem. 66, 667–675.

    Article  PubMed  CAS  Google Scholar 

  • Hucho F., Oberthur W., and Lottspeich F. (1986) The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices MII of the receptor subunits.FEBS Lett. 205, 137–142.

    Article  PubMed  CAS  Google Scholar 

  • Hughes J. and Hatsukami D. (1986) Signs and symptoms of tobacco withdrawal.Arch. Gen. Psych. 43, 289–294.

    CAS  Google Scholar 

  • Kao P. and Karlin A. (1986) Acetylcholine receptor binding site contains a disulfide crosslink between adjacent half-cystinyl residues.J. Biol. Chem. 261, 8085–8088.

    PubMed  CAS  Google Scholar 

  • Karlin A. and Akabas M. (1995) Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.Neuron 15, 1231–1244.

    Article  PubMed  CAS  Google Scholar 

  • Karlin A., Holtzman E., Yodh N., Label P., Wall J., and Hainfeld J. (1983) The arrangement of the subunits of the acetylcholine receptor of Torpedo californica.J. Biol. Chem. 258, 6678–6681.

    PubMed  CAS  Google Scholar 

  • Kennedy L. (1996) Nicotinic therapy for ulcerative colitis.Ann. Pharmacother. 30, 1022–1023.

    PubMed  CAS  Google Scholar 

  • Keyser K., Britto L., Schoepfer R., Whiting P., Cooper J., Conroy W., Brozozowska-Pretchtl A., Karten H., and Lindstrom J. (1993) Three subtypes of αbungarotoxinsensitive nicotinic acetylcholine receptors are expressed in chick retina.J. Neurosci. 13, 442–454.

    PubMed  CAS  Google Scholar 

  • Kihara T., Shimohama S., Sawada H., Kimura J., Kume T., Kochiyama H., Maeda T., and Akaike A. (1997) Nicotinic receptor stimulation protects neurons against β amyloid toxicity.Ann. Neurol. 42, 159–163.

    Article  PubMed  CAS  Google Scholar 

  • Koop C. (1988) The health consequences of smoking. Nicotine addiction. A report of the Surgeon General, U.S. Dept. of Health and Human Services.

  • Kuryatov A., Gerzanich V., Nelson M., Olale F., and Lindstrom J. (1997) Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca++ permeability, conductance, and gating of human α4β2 nicotinic acetylcholine receptors,J. Neurosci, in press.

  • Lang B., Waterman S., Pinto A., Janes D., Boot J., Vincent A., and Newsome-David J. (1997) The role of autoantibodies in Lambert-Eaton myasthenic syndrome (LEMS).Ann. NY Acad. Sci. IX International Conference on Myasthenia Gravis and Related Disorders, in press.

  • Lange K., Wells F., Jenner P., and Marsden P. (1993) Altered muscarinic and nicotinic receptor densities in cortical and subcortical regions in Parkinson's disease.J. Neurochem. 60, 197–203.

    Article  PubMed  CAS  Google Scholar 

  • Lena C. and Changeux J. (1997) Role of Ca++ ions in nicotinic facilitation of GABA release in mouse thalamus.J. Neurosci. 17, 576–586.

    PubMed  CAS  Google Scholar 

  • Lennon, V., Griesmann G., Sciamanna M., and Wieben E. (1997). Lung carcinoma, cation channel autoimmunity and paraneoplastic myasthenic syndromes.Ann. NY Acad. Sci. IX International Conference on Myasthenia Gravis and Related Disorders, in press.

  • LeNovere N. and Changeux J. (1995) Molecular evolution of the nicotinic acetylcholine receptor, an example of a multigene family in excitable cells.J. Mol. Evol. 40, 155–172.

    Article  CAS  Google Scholar 

  • LeNovere N., Zoli M., and Changeux J. (1996) Neuronal nicotinic receptor α6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain.Eur. J. Neurosci. 8, 2428–2439.

    Article  CAS  Google Scholar 

  • Leonard S., Adams C., Breese C., Adler L., Bickford P., Byerley W., Coon H., Griffith J., Miller C., Myles-Worsley M., Nagamoto H., Rollins Y., Stevens K., Waldo M., and Freedman R. (1996) Nicotinic receptor function in schizophrenia.Schizophren. Bull. 22, 431–445.

    CAS  Google Scholar 

  • Lindstrom J. (1996) Neuronal nicotinic acetylcholine receptors, inIon Channels, vol. 4 (Toshio N., ed.), Plenum, New York, pp. 377–450.

    Google Scholar 

  • Lindstrom J., Anand R., Peng X., Gerzanich V., Wang F., and Li Y. (1995) Neuronal nicotinic receptor subtypes, inFunctional Diversity of Interacting Receptors, vol. 757 (Lajtha A. and Abood L., eds.), New York Academy of Science, New York, pp. 100–116.

    Google Scholar 

  • Lindstrom J., Merlie J., and Yogeeswaran B. (1979) Biochemical properties of acetylcholine receptor subunits fromTorpedo californica.Biochemistry 18, 4465–4470.

    Article  PubMed  CAS  Google Scholar 

  • Lindstrom J., Peng X., Kuryatov A., Lee E., Anand R., Gerzanich V., Wang F., Wells G., and Nelson M. (1997) Molecular and antigenic structure of nicotinic acetylcholine receptors,Ann. NY Acad. Sci. Proceedings of IX International Conference on Myasthenia Gravis and Related Disorders, in press.

  • Lindstrom J., Shelton G., and Fujii Y. (1988) Myasthenia gravis.Adv. Immunol. 42, 233–284.

    PubMed  CAS  Google Scholar 

  • Lipton S. and Kater S. (1989) Neurotransmitter regulation of neuronal outgrowth plasticity, and survival.TINS 12, 265–270.

    PubMed  CAS  Google Scholar 

  • Little H. (1991) Mechanisms that may underlie the behavioral effects of ethanol.Prog. Neurobiol. 36, 171–194.

    Article  PubMed  CAS  Google Scholar 

  • Lloyd G., Davidson L., and Hornykiewicz O. (1975) The neurochemistry of Parkinson's disease, effect of L-DOPA therapy.J. Pharmacol. Exp. Ther. 195, 453–464.

    PubMed  CAS  Google Scholar 

  • Lloyd G. (1996) Subtype selective nicotinic receptor agonists for the treatment of the motor and nonmotor dysfunctions of Parkinson's disease.Movement. Dis. 11, 25.

    Google Scholar 

  • Lukas R. (1991) The effects of chronic nicotinic ligand exposure on functional activity of nicotinic acetylcholine receptors expressed by cells of the PC12 rat pheochromocytoma or the TE671/RD human clonal line.J. Neurochem. 56, 1134–1145.

    Article  PubMed  CAS  Google Scholar 

  • Luther M., Schoepfer R., Whiting P., Blatt Y., Montal M., Montal M., and Lindstrom J. (1989) A muscle acetylcholine receptor, is expressed in the human cerebellar medullablastoma cell line TE671.J. Neurosci. 9, 1082–1096.

    PubMed  CAS  Google Scholar 

  • Ma C., Zhang G., Xiao B., Link J., Olsson T., and Link H. (1995) Suppression of experimental autoimmune myasthenia gravis by nasal administration of acetylcholine receptor.J. Neuroimmunol. 58, 51–60.

    Article  PubMed  CAS  Google Scholar 

  • Ma C., Zhang G., Xiao B., Wang Z. Link J., Olsson T., and Link T. (1996) Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-γ-expressing Th1-like cells and upregulation of TGF-β mRNA in mononuclear cells.Ann. NY Acad. Sci. 778, 273–287.

    Article  PubMed  CAS  Google Scholar 

  • Magleby K. (1996) Neuromuscular transmission, inMyology, 2nd ed., vol. 1 (Engel A. and Franzini-Armstrong C., eds.), McGraw Hill, New York, pp. 442–463.

    Google Scholar 

  • Marks M., Pauly J., Gross D., Deneris E., Hermans-Borgmeyer I., Heinemann S., and Collins A. (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment.J. Neurosci. 12, 2765–2784.

    PubMed  CAS  Google Scholar 

  • Martin M., Czajkowski C., and Karlin A. (1996) The contribution of aspartyl residues in the acetylcholine receptor γ and δ subunits to the binding of agonists and competitive antagonists.J. Biol. Chem. 271, 13,497–13,503.

    CAS  Google Scholar 

  • Martin E., Panickar K., King M., Deyrup M., Hunterm B., Wang G., and Meyer E. (1994) Cytoprotective actions of 2, 4 dimethoxybenzlidene anabaseine in differentiated PC12 cells and septal cholinergic neurons.Drug Develop. Res. 31, 135–141.

    Article  CAS  Google Scholar 

  • McGehee D. and Role L. (1995) Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons.Annu. Rev. Physiol. 57, 521–546.

    Article  PubMed  CAS  Google Scholar 

  • Meldrum B. and Garthwaite J. (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease.Trends Pharmacol. Sci. 11, 379–387.

    Article  PubMed  CAS  Google Scholar 

  • Menzaghi F., Whelan K., Risbrough V., Rao T., and Lloyd G. (1997a) Effects of a novel cholinergic ion channel agonist SIB-1765F on locomotor activity in rats.J. Pharmacol. Exp. Ther. 280, 384–392.

    PubMed  CAS  Google Scholar 

  • Menzaghi F., Whelan K., Risbrough V., Rao T., and Lloyd G. (1997b) Interactions between a novel cholinergic ion channel agonist, SIB-1765F and L-DOPA in the reserpine model of Parkinson's disease in rats.J. Pharmacol. Exp. Ther. 280, 393–401.

    PubMed  CAS  Google Scholar 

  • Messi M., Renganathan M., Grigorenko E., and Delbono O. (1997) Activation of α7 nicotinic acetylcholine receptor promotes survival of spinal cord motoneurons.FEBS Lett. 411, 32–38.

    Article  PubMed  CAS  Google Scholar 

  • Meyer E., deFiebre C., Hunter B., Simpkins C., Franworth N., and deFiebre N. (1994) Effects of anabaseine-related analogs on rat brain nicotinic receptor binding and on avoidance behaviors.Drug. Develop. Res. 31, 127–134.

    Article  CAS  Google Scholar 

  • Mihovilovic M. and Roses A. (1993) Expression of α3, α5, and β4 neuronal acetylcholine receptor subunit transcripts in normal and myasthenia gravis thymus.J. Immunol. 151, 6517–6524.

    PubMed  CAS  Google Scholar 

  • Milone, M., Ohno K., and Wang H. (1996) Novel slow channel syndrome due to mutation in the acetylcholine receptor α subunit with increased conductance, nanomolar affinity for acetylcholine, and prolonged open durations of the AChR channel.Ann. Neurol. 40, 956

    Google Scholar 

  • Morens D., Grandinetti A., Reed D., White L., and Ross G. (1995) Cigarette smoking and protection from Parkinson's disease, false association or etiologic clue.Neurology 45, 1041–1051.

    PubMed  CAS  Google Scholar 

  • Nagata K., Aistrup G., Huang C., Marszalec W., Song J., Yeh J., and Narahashi T. (1996) Potent modulation of neuronal nicotinic acetylcholine receptor channel by ethanol.Neurosci. Letters 217, 189–193.

    Article  CAS  Google Scholar 

  • Newhouse P., Potter A., and Lenox E. (1993) The effects of nicotinic agents on human cognition, possible therapeutic applications in Alzheimer's and Parkinson's diseases.Med. Chem. Res. 2, 628–642.

    CAS  Google Scholar 

  • Newsome-Davis J. and Vincent A. (1991) Antibody mediated neurological disease.Curr. Opin. Neurobiol. 1, 430–435.

    Article  Google Scholar 

  • Noda M., Furutani Y., Takahashi H., Toyosato M., Tanabe T., Shimizu S., Kikyotani S., Kayano T., Hirose T., Inayama S., and Numa S. (1983) Cloning and sequence analysis of calf cDNA and human genomic DNA encoding α subunit precursor of muscle acetylcholine receptor.Nature 305, 818–823.

    Article  PubMed  CAS  Google Scholar 

  • Ohno K., Hutchinson D., Milone M., Brengman J., Bonzat C., Sine S., and Engel A. (1995) Congenital myasthenia syndrome caused by prolonged acetylcholine receptor channel openings due to a mutations in the M2 domain of the ε subunit.Proc. Natl. Acad. Sci. USA 92, 758–762.

    Article  PubMed  CAS  Google Scholar 

  • Ohno K., Wang H., Milone M., Bren N., Brengman J., Nakano S., Quiram P., Pruitt J., Sine S., and Engel A. (1996) Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor ε subunit.Neuron 17, 157–170.

    Article  PubMed  CAS  Google Scholar 

  • Ohno K., Quiram P., Milone M., Wang H., Harper M., Pruitt J., Brengman J., Pao L., Fischbeck K., Crawford T., Sine S., and Engel A. (1997) Congenital myasthenic syndromes due to heteroallelic nonsense/missence mutations in the acetylcholine receptor ε subunit gene, identification and functional characterization of six new mutations.Human Mol. Genet. 6, 753–766.

    Article  CAS  Google Scholar 

  • Okamura S., McIntosh K., and Drachman D. (1994) Oral administration of acetylcholine receptor, effects on experimental myasthenia gravis.Ann. Neurol. 36, 704–713.

    Article  Google Scholar 

  • Olale F., Gerzanich V., Kuryatov A., Wang F., and Lindstrom J. (1997) Chronic nicotine exposure differentially affects the function of human α3, α4, and α7 neuronal nicotinic receptor subtypes, submitted for publication.

  • O'Leary M., Filatov G., and White M. (1994) Characterization of d-tubocurarine binding site of Torpedo acetylcholine receptor.Am. J. Physiol. 266, c648-c653.

    PubMed  Google Scholar 

  • Orr-Urtreger A., Goldmer F., Patrick, J., and Beadet A. (1996) Generation of mice deficient in the α7 neuronal nicotinic receptor gene by targeted recombination.Neurosci. Soc. Meeting. Abst. 501, 6.

    Google Scholar 

  • Papke R. (1993) The kinetic properties of neuronal nicotinic receptor genetic basis of functional diversity.Prog. Neurobiol. 41, 509–531.

    Article  PubMed  CAS  Google Scholar 

  • Papke R., deFiebre C., Kem W., and Meyer E. (1994) The subunit specific effects of novel anabasinederived nicotinic agents, inAlzheimer Disease, Therapeutic Strategies (Giacobini E. and Becker R., eds.), Birkhauser, Boston, MA, pp. 206–211.

    Google Scholar 

  • Pauly J., Marks M., Robinson S., van de Kamp J., and Collins A. (1996) Chronic nicotine and mecamylamine treatment increase brain nicotinic receptor binding without changing α4 or β2 mRNA levels.J. Pharmacol. Exp. Ther. 278, 361–369.

    PubMed  CAS  Google Scholar 

  • Pederson S. and Cohen J. (1990) d-tubcurarine binding sites are located at α-γ and α-δ subunit interfaces of the nicotinic acetylcholine receptor.Proc. Natl. Acad. Sci. USA 87, 2785–2789.

    Article  Google Scholar 

  • Peng X., Anand R., Whiting P., and Lindstrom J. (1994a) Nicotine-induced upregulation of neuronal nicotinic receptors results from a decrease in the rate of turnover.Mol. Pharmacol. 46, 523–530.

    PubMed  CAS  Google Scholar 

  • Peng X., Katz M., Gerzanich V., Anand R., and Lindstrom J. (1994b) Human α7 acetylcholine receptor, cloning of the α7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional α7 homomers expressed inXenopus oocytes.Mol. Pharmacol. 45, 546–554.

    PubMed  CAS  Google Scholar 

  • Peng X., Gerzanich V., Anand R., Wang F., and Lindstrom J. (1997) Chronic nicotine treatment upregulates α3 AChRs and α7 AChRs expressed by the human neuroblastoma cell line SH-SY5Y.Mol. Pharmacol. 51, 776–784.

    PubMed  CAS  Google Scholar 

  • Perkins K., Sexton J., and Di Marco A. (1996) Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers.Physiol. and Behav. 60, 305–309.

    Article  CAS  Google Scholar 

  • Perry E., Morris, C., Court J., Cheng A., Fairbairn A., McKeith I., Irving D., Brown A., and Perry R. (1995) Alteration in nicotine binding sites in Parkinson's disease, Lewy Body Dementia and Alzheimer's disease, possible index of early neuropathology.Neuroscience 64, 385–395.

    Article  PubMed  CAS  Google Scholar 

  • Peto R., Lopez A., Boreham J., Thun M., and Heath C. (1992) Mortality from tobacco in developed countries, indirect estimation from national vital statistics.Lancet 389, 1268–1278.

    Article  Google Scholar 

  • Picciotto M., Zoll M., Lena C., Bessis A., Lallemand Y., LeNovere M., Vincent P., Pich M., Brulet P., and Changeux J. (1995) Abnormal avoidance learning in mice lacking functional high affinity nicotine receptor in the brain.Nature 374, 65–67.

    Article  PubMed  CAS  Google Scholar 

  • Pich E., Pagluisi S., Tessari M., Talabot-Ayer D., Huiysdujnen R., and Chiamulera C. (1997) Common neural sustates for the addictive properties of nicotine and cocaine.Science 275, 83–86.

    Article  PubMed  CAS  Google Scholar 

  • Potthoff A., Ellison G., and Nelson L. (1983) Ethanol intake increases during continuous administration of amphetamine and nicotine, but not several other drugs.Pharmacol. Biochem. Behav. 18, 489–493.

    Article  PubMed  CAS  Google Scholar 

  • Pugh P. and Berg D. (1994) Neuronal acetylcholine receptors that bind αbungarotoxin mediate neurite retraction in a calcium-dependent manner.J. Neurosci. 14, 889–896.

    PubMed  CAS  Google Scholar 

  • Quick M. (1995) Growth related role for the nicotinic αbungarotoxin receptor, inEffects of Nicotine on Biological Systems II (Clarke P., Quik M., Adlkofer F., Thurau K., eds.), Kirkhauser, Basel, pp. 145–150.

    Google Scholar 

  • Raftery M., Hunkapillar M., Strader C., and Hood L. (1980) Acetylcholine receptor, complex of homologous subunits.Science 208, 1454–1457.

    Article  PubMed  CAS  Google Scholar 

  • Ramirez-Latorre J., Yu C., Qu X., Perin F., Karlin A., and Role L. (1996) Functional contributions of α5 subunit to neuronal acetylcholine receptor channels.Nature 380, 347–351.

    Article  PubMed  CAS  Google Scholar 

  • Rathouz M., Vijayaraghavan S., and Berg D. (1995) Acetylcholine differentially affects intracellular calcium via nicotinic and muscarinic receptors on the same population of neurons.J. Biol. Chem. 270, 14,366–14,375.

    CAS  Google Scholar 

  • Reynolds J. and Karlin A. (1978) Molecular weight in detergent solution of acetylcholine receptor fromTorpedo californica.Biochemistry 17, 2035–2038.

    Article  PubMed  CAS  Google Scholar 

  • Role L. and Berg D. (1996) Nicotinic receptors in the development and modulation of CNS synapses.Neuron 16, 1077–1085.

    Article  PubMed  CAS  Google Scholar 

  • Romano S., Corriveau R., Schwarz R., and Berg D. (1997a) Expression of the nicotinic receptor α7 gene in tendon and periosteum during early development.J. Neurochem. 68, 640–648.

    Article  PubMed  CAS  Google Scholar 

  • Romano S., Pugh P., McIntosh J., and Berg D. (1997b) Neuronal-type acetylcholine receptors and regulation of α7 gene expression in vertebrate skeletal muscle.J. Neurobiol. 32, 69–80.

    Article  PubMed  CAS  Google Scholar 

  • Rose J., Levin E., Behm F., Westman E., Stein R., Lane J., and Ripka G. (1995) Combined administration of agonist-antagonist as a method of regulating receptor activation.Ann. NY Acad. Sci. 757, 218–221.

    Article  PubMed  CAS  Google Scholar 

  • Sacaan A., Reid R., Santori E., Adams P., Correa L., Mahaffy L., Bleicher L., Cosford N., Stauderman K., McDonald I., Rao T., and Lloyd G. (1997) Pharmacological characterization of SIB-1765F, a novel cholinergic ion channel agonist.J. Pharmacol. Exp. Ther. 280, 373–383.

    PubMed  CAS  Google Scholar 

  • Saedi M., Anand R., Conroy W., and Lindstrom J. (1990) Determination of amino acids critical to the main immunogenic region of intact acetylcholine receptors by in vitro mutagenesis.FEBS Lett. 267, 55–59.

    Article  PubMed  CAS  Google Scholar 

  • Sahakian B., Janes G., Levy M., and Warburton D. (1989) The effect of nicotine on attention, information processing, and short term memory in patients with dementia of the Alzheimer type.Brit. J. Psych. 154, 797–800.

    CAS  Google Scholar 

  • Sanberg P., Silver R., Shuttle R., et al. (1997) Nicotine for the treatment of Tourette's syndrome.Pharmacol. Ther. 74, 21–25.

    Article  PubMed  CAS  Google Scholar 

  • Sargent P. (1993) The diversity of neuronal nicotinic acetylcholine receptors.Annu. Rev. Neurosci. 16, 403–443.

    Article  PubMed  CAS  Google Scholar 

  • Sastry R. and Sadavongivad C. (1979) Cholinergic systems in non-nervous tissues.Pharmacol. Rev. 30, 66–132.

    Google Scholar 

  • Scheffer I., Bhatia K., Lopes-Cendes I., Fish D., Marsden C., Andermann E., Desbiens R., Keene D., Cendes F., Manson J., Constantinou J., McIntosh A., and Berkovic S. (1995) Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder.Brain 118, 61–73.

    Article  PubMed  Google Scholar 

  • Schluep M., Willcox N., Vincent A., Dhoot G., and Newson-Davis J. (1987) Acetylcholine receptors in human thymic myoid cells in situ, an immunohistological study.Ann. Neurol. 22, 212–222.

    Article  PubMed  CAS  Google Scholar 

  • Schoepfer R., Conroy W., 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 superfamily.Neuron 5, 35–48.

    Article  PubMed  CAS  Google Scholar 

  • Schuller H. (1995) Mechanisms of nicotine stimulated cell proliferation in normal and neoplastic neuroendocrine lung cells, inEffects of Nicotine on Biological Systems II (Clarke P., Quick M., Adelkofer F., and Thurau K., eds.), Birkhauser Verlag, Basel, pp. 151–158.

    Google Scholar 

  • Schwartz R. and Kellar K. (1983) Nicotinic cholinergic receptor binding sites in the brain, regulation in vivo.Science 220, 214–216.

    Article  PubMed  CAS  Google Scholar 

  • Seguela P., wadiche J., Dinnelly-Millet K., Dani J., and Patrick J. (1993) Molecular cloning, functional properties, and distribution of rat brain α7, a nicotinic cation channel highly permeable to calcium.J. Neurosci. 13, 596–604.

    PubMed  CAS  Google Scholar 

  • Sher E. and Clementi F. (1997) Neuronal ion channels in lung cancer cells, role in mitogenesis and autoimmunity,Ann. NY Acad. Sci. IX International Conference on Myasthenia Gravis and Related Disorders, in press.

  • Shimohama S., Akaike A., and Kimura J. (1996) Nicotine-induced cholinergic receptor-mediated inhibition of nitric oxide formation.Ann. NY Acad. Sci. 777, 356–361.

    Article  PubMed  CAS  Google Scholar 

  • Silver A., Shytle R., Philip M., and Sanberg P. (1995) Transdermal nicotine in Tourette's syndrome, inEffects of Nicotine on Biological Systems II (Clarke P. Quick M., Adelkofer F., Thurau K., eds.), Birkhauser, Basel, pp. 293–299.

    Google Scholar 

  • Sine S. (1993) Molecular dissection of subunit interfaces in the acetylcholine receptor, identification of residues that determine curare selectivity.Proc. Natl. Acad. Sci. USA 90, 9436–9440.

    Article  PubMed  CAS  Google Scholar 

  • Sine S., Kreienkamp H., Bren N., Maeda R., and Taylor P. (1995) Molecular dissection of subunit interfaces in the acetylcholine receptor, identification of determinants of α-conotoxin M1 selectivity.Neuron 15, 205–211.

    Article  PubMed  CAS  Google Scholar 

  • Sine S., Ohno K., Bouzat C., Auerbach A., Milone M., Pruitt J., and Engel A. (1995) Mutation of the acetylcholine receptors α subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity.Neuron 15, 229–239.

    Article  PubMed  CAS  Google Scholar 

  • Steinlein O., Magnusson A., Stoodt J., Bertrand S., Weiland S., Berkovic S., Nakken K., Propping P., and Bertrand D. (1997) An insertion mutation of the CHRNA 4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy.Human Mol. Genetics 6, 943–947.

    Article  CAS  Google Scholar 

  • Steinlein O., Mulley J., Propping P., Wallace R., Phillips H., sutherland G., Scheffer I., and Berkovic S. (1995) Amissense mutation in the neuronal nicotinic acetylcholine receptor α4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.Nature Genet. 11, 201–203.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Tarroni P., Rubboli F., Chini B., Zwatt R., Oortgiesen M., Sher E., and Clementi F. (1992) Neuronal-type nicotinic receptors in human neuroblastoma and small cell carcinoma cell lines.FEBS Lett. 312, 66–70.

    Article  PubMed  CAS  Google Scholar 

  • Thomas G. and Rhodes J. (1995) Relationship between smoking, nicotine, and ulcerative coli-tis, inEffects of Nicotine on Biological Systems II Advances in Pharmacological Sciences (Clarke P., Quick M., Adelkofer F., and Thurau K., eds.), Birkhauser, Boston, pp. 287–291.

    Google Scholar 

  • Tzartos S., Cung M., Demange P., Loutrari H., Mamalaki A., Marraud M., Papadouli I., Sakarellos C., and Tsikaris V. (1991) The main immunogenic region (MIR) of the nicotinic acetylcholine receptor and the anti-MIR antibodies.Mol. Neurobiol. 5, 1–29.

    Article  PubMed  CAS  Google Scholar 

  • Tzartos, S., Hochschwender S., Vasquez P., and Lindstrom J. (1987) Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor.J. Neuroimmunol. 15, 185–194.

    Article  PubMed  CAS  Google Scholar 

  • Tzartos S., Seybold M., and Lindstrom J. (1982) Specificity of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies.Proc. Natl. Acad. Sci. USA 79, 188–192.

    Article  PubMed  CAS  Google Scholar 

  • Ullian E. and Sargent P. (1995) Pronounced cellular diversity and extrasynaptic location of nicotinic acetylcholine receptor subunit immunoreactivities in the chicken pretectum.J. Neurosci. 15, 7012–7023.

    PubMed  CAS  Google Scholar 

  • Unwin N. (1993) Nicotinic acetylcholine receptor at 9Å resolution.J. Mol. Biol. 229, 1101–1124.

    Article  PubMed  CAS  Google Scholar 

  • Unwin N. (1995) Acetylcholine receptor channel imaged in the open state.Nature 373, 37–43.

    Article  PubMed  CAS  Google Scholar 

  • Vernalis A., Conroy W., and Berg D. (1993) Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes.Neuron 10, 451–464.

    Article  Google Scholar 

  • Vijayaraghavan S., Rathouz M., Pugh P., and Berg D. (1992) Nicotinic receptors that bind α bungarotoxin on neurons raise intracellular free Ca++.Neuron 8, 353–362.

    Article  PubMed  CAS  Google Scholar 

  • Vincent A., Lang B., and Newsom-Davis J. (1989) Autoimmunity to the voltage-gated calcium channel underlies the Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder.TINS 12, 496–502.

    PubMed  CAS  Google Scholar 

  • Vincent A., Newland C., Brueton L., Beeson D., Riemersma S., Huson S., and Newsom-Davis J. (1995) Arthrogryposis multiplex congenita with maternal autoantibodies specific for a fetal antigen.Lancet 346, 24–25.

    Article  PubMed  CAS  Google Scholar 

  • Violet J., Downie D., Nakisa R., Lieb W., and Franks N. (1997) Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics.Anesthesiology 86, 866–874.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z., Hardy S., and Hall Z. (1996) Assembly of the nicotinic acetylcholine receptor.J. Biol. Chem. 271, 27,575–27,584.

    CAS  Google Scholar 

  • Wang F., Gerzanich V., Wells G., Anand R., Peng X., Keyser K., and Lindstrom J. (1996) Assembly of human neuronal nicotinic receptor α5 subunits with α3, β2, and β4 subunits.J. Biol. Chem. 271, 17,656–17,665.

    CAS  Google Scholar 

  • Wang Z., Huang J., Olsson T., He S., and Link H. (1995) B cell responses to acetylcholine receptor in rats orally tolerized against experimental autoimmune myasthenia gravis.J. Neurol. Sci. 128, 167–174.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z., Link H., Ljungdahl A., Hojeberg B., Link J. He B., Qiao J., Melms A., and Olsson T. (1994) Induction of interferon-γ, interleukin-4, and transforming growth factor-β in rats orally tolerized against experimental autoimmune myasthenia gravis.Cell. Immunol. 157, 353–368.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z., Qiao J., and Link H. (1993a) Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor.J. Neuroimmunol. 44, 209–214.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z., Qiao J., Melms A., and Link H. (1993b) T cell reactivity to acetylcholine receptor in rats orally tolerized against experimental autoimmune myasthenia gravis.Cell. Immunol. 152, 394–404.

    Article  PubMed  CAS  Google Scholar 

  • Watson J. and Lewis R. (1995) Ulcerative colitis response to smoking and to nicotine chewing gum in a patient with α1 anti-trypsin deficiency.Res. Med. 89, 635–636.

    Article  CAS  Google Scholar 

  • Weight F., Peoples R., Wright J., Li C., Aguaya L., Lovinger D., and White G. (1993) Neurotransmiter-gated ion channel as molecular sites of alcohol action, inAlcohol, Cell Membranes and Surgical Transduction in Brain (Alling C., Diamond I., and Lelsie S., eds.), Plenum, New York, pp. 107–122.

    Google Scholar 

  • Weiland S., Weitzmann V., Villarroel A., Propping P., and Steinlein O. (1996) An amino acid exchange in the second transmembrane segment of a neuronal nicotinic receptor causes partial epilepsy by altering its desensitization kinetics.FEBS Lett. 398, 91–96.

    Article  PubMed  CAS  Google Scholar 

  • Weiner H. (1997) Oral tolerance for the treatment of autoimmune diseases.Ann. Rev. Med. 48, 341–351.

    Article  PubMed  CAS  Google Scholar 

  • Wenger B., Bryant D., Boyd T., and McKay D. (1997) Evidence for spare nicotinic acetylcholine receptors of a β4 subunit in bovine adrenal chromaffin cells, studies using bromoacetylcholine, epibatidine, cysteine, and mAb35.J. Pharmacol. Exp. Ther. 281, 905–913.

    PubMed  CAS  Google Scholar 

  • Whitehouse P., Matino A., Marcus K., Zweig R., Singer H., Price D., and Kellar K. (1988) Reduction in acetylcholine and nicotine binding in several degenerative diseases.Arch. Neurol. 45, 722–724.

    PubMed  CAS  Google Scholar 

  • Whiting P., Cooper J., and Lindstrom J. (1987) Antibodies in sera from patients with myasthenia gravis do not bind to acetylcholine reeptors from human brain.J. Neuroimmunol. 16, 205–213.

    Article  PubMed  CAS  Google Scholar 

  • Whiting P. and Lindstrom J. (1988) Characterization of bovine and human neuronal nicotinic acetylcholine receptors using monoclonal antibodies.J. Neurosci. 8, 3395–3404.

    PubMed  CAS  Google Scholar 

  • Williamson D., Madans J., Anda R., Kleinman J., Giovino G., and Byers T. (1991) Smoking cessation and severity of weight gain in a national cohort.N. Engl. J. Med. 324, 739–745.

    Article  PubMed  CAS  Google Scholar 

  • 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, 347–448.

    Article  Google Scholar 

  • Wonnacott S. (1997) Presynaptic nicotinic ACh receptors.TINS 20, 92–98.

    PubMed  CAS  Google Scholar 

  • Yu D., Zhang L., Eisele J., Bertrand D., and Changeux J. (1996) Ethanol inhibition of nicotinic acetylcholine type α7 receptors involves the amino-terminal domain of the receptor.Mol. Pharmacol. 50, 1010–1016.

    PubMed  CAS  Google Scholar 

  • Zhang Z., Coggan J., and Berg D. (1996) Synaptic currents generated by neuronal acetylcholine receptors sensitive to α bungarotoxin.Neuron 17, 1231–1240.

    Article  PubMed  CAS  Google Scholar 

  • Zhang L., Oz M., Stewart R., Peoples R., and Weight F. (1997) Volatile general anesthetic actions on recombinant nAChα7, 5-HT3 and chimeric nAChα7-5-HT3 receptors expressed inXenopus oocytes.Brit. J. Pharmacol. 120, 353–355.

    Article  CAS  Google Scholar 

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Lindstrom, J. Nicotinic acetylcholine receptors in health and disease. Mol Neurobiol 15, 193–222 (1997). https://doi.org/10.1007/BF02740634

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