Skip to main content
SpringerLink
Log in

Nicotinic Acetylcholine Receptors and Low Molecular Weight Toxins

  • Chapter
Selective Neurotoxicity

Part of the book series: Springer Study Edition ((SSE,volume 102))

  • 101 Accesses

Abstract

The study of the nicotinic acetylcholine receptor has since its very inception been associated with the use of toxins. The work by Langley in 1905 demonstrated (amongst many important and lasting findings) the presence of the “receptive substance” in striated muscle and sympathetic ganglia. Indeed, the receptor was named for its responsiveness to the tobacco alkaloid nicotine. Although the physiological transmitter in these and other tissues was later identified as acetylcholine (ACh), this receptor has been classically distinguished from other cholinergic receptors by their responses to nicotine and muscarine (Dale 1914). Langley also offered a precocious description of multiple sites or multiple ways in which a toxin might produce both agonist and antagonist effects:

This work was supported by NIH Grant NS 25296 and U.S. Army Medical Research and Development Command Contract DAMD17-88-C-8819.

To whom reprint requests should be sent.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abramson SN, Li Y, Culver P, Taylor P (1989) An analog of lophotoxin reacts covalently with Tyr190 in the α-subunit of the nicotinic acetylcholine receptor. J Biol Chem 264:12666–12672

    PubMed  CAS  Google Scholar 

  • Adams DJ (1983) Chemical modification of endplate channels in frog skeletal muscle. J Physiol (Lond) 343:29P

    Google Scholar 

  • Adams PR (1972) Voltage jump analysis of procaine action at frog end-plate. J Physiol (Lond) 268:291–318

    Google Scholar 

  • Adams PR, Sakmann B (1978) Decamethonium both opens and blocks endplate channels. Proc Natl Acad Sci USA 75:2994–2998

    PubMed  CAS  Google Scholar 

  • Adler M, Albuquerque EX, Lebeda FJ (1978) Kinetic analysis of endplate currents altered by atropine and scopolamine. Mol Pharmacol 14:514–529

    PubMed  CAS  Google Scholar 

  • Adler M, Oliveira AC, Albuquerque EX, Mansour NA, Eldefrawi AT (1979) Reaction of tetraethylammonium with the open and closed conformations of the acetylcholine receptor ionic channel complex. J Gen Physiol 74:129–152

    PubMed  CAS  Google Scholar 

  • Aguayo LG, Albuquerque EX (1986) Effects of phencyclidine and its analogs on the end-plate current of the neuromuscular junction. J Pharmacol Exp Ther 239:15–24

    PubMed  CAS  Google Scholar 

  • Akaike A, Ikeda SR, Brookes N, Pascuzzo GJ, Rickett DL, Albuquerque EX (1984) The nature of the interaction of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. II. Patch clamp studies. Mol Pharmacol 25:102–112

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Spivak CE (1984) Natural toxins and their analogues that activate and block the ionic channel of the nicotinic acetylcholine receptor. In: Krogsgaard-Larsen P, Brogger Christenses S, Kofod H (eds) Natural products and drug development. Munksgaard, Copenhagen, pp 301–323 (Alfred Benzon symposium, vol 20

    Google Scholar 

  • Albuquerque EX, Barnard EA, Chiu TH, Lapa AJ, Dolly JO, Jansson S-E, Witkop B (1973a) Acetylcholine receptor and ion conductance modulator sites at the murine neuromuscular junction: evidence from specific toxin reactions. Proc Natl Acad Sci USA 70:949–953

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Kuba K, Lapa AJ, Daly JW, Witkop B (1973b) Acetylcholine receptor and ionic conductance modulator of innervated and denervated muscle membranes. Effect of histrionicotoxins. Excerpta Med Int Cong Ser 333:585–597

    Google Scholar 

  • Albuquerque EX, Barnard EA, Porter CW, Wärnick JE (1974) The density of acetylcholine receptors and their sensitivity In the postsynaptic membrane of muscle endplates. Proc Natl Acad Sci USA 71:2818–2822

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Akaike A, Shaw K-P, Rickett DL (1984) The interaction of anticholinesterase agents with the acetylcholine receptor-ionic channel complex. Fund Appl Toxicol 4:S27–S33

    CAS  Google Scholar 

  • Albuquerque EX, Deshpande SS, Kawabuchi M, Aracava Y, Idriss M, Rickett DL, Boyne AF (1985) Multiple actions of anticholinesterase agents on chemosensitive synapses: molecular basis for prophylaxis and treatment of organophosphate poisoning. Fundam Appl Toxicol 5:S182–S203

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Deshpande SS, Aracava Y, Alkondon M, Daly JW (1986) A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor. A study with forskolin and its analogs. FEBS Lett 199:113–120

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Swanson KL, Deshpande SS, Aracava Y, Cintra WM, Kawabuchi M, Alkondon M (1987) The direct interaction of Cholinesterase inhibitors with the acetylcholine receptor and their involvement with cholinergic autoregulatory mechanisms. In: Sixth Medical Chemical Defense Bioscience Review US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, pp 27–34

    Google Scholar 

  • Albuquerque EX, Aguayo L, Swanson KL, Idriss M, Warnick JE (1988a) Multiple interactions of phencyclidine at central and peripheral sites. In: Domino EF, Kamenka J-M (eds) Sigma and phencyclidine-like compounds as molecular probes in biology. NPP, Ann Arbor, pp 425–438

    Google Scholar 

  • Albuquerque EX, Alkondon M, Deshpande SS, Cintra WM, Aracava Y, Brossi A (1988b) The role of carbamates and oximes in reversing toxicity of organophosphorus compounds: a perspective into mechanisms. In: Lunt GG (ed) Neurotox ’88: molecular basis of drug and pesticide action. Elsevier, Cambridge, pp 349–373

    Google Scholar 

  • Albuquerque EX, Aracava Y, Cintra WM, Brossi A, Schönenberger B, Deshpande SS (1988c) Structure-activity relationship of reversible Cholinesterase inhibitors: activation, channel blockade and stereospecificity of the nicotinic acetylcholine receptor-ion channel complex. Braz J Med Biol Res 21:1173–1196

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Daly JW, Warnick JE (1988d) Macromolecular sites for specific neurotoxins and drugs on chemosensitive synapses and electrical excitation in biological membranes. Ion Channels 1:95–162

    PubMed  CAS  Google Scholar 

  • Albuquerque EX, Maelicke A, Pereira EFR (1991) Single channel currents activated by physostigmine in hippocampal neurons are blocked by benzoquinonium but not by methyllycaconitine. Soc Neurosci Abs 17:585

    Google Scholar 

  • Alkondon M, Albuquerque EX (1990) α-Cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons. Eur J Pharmacol 191:505–506

    PubMed  CAS  Google Scholar 

  • Alkondon M, Albuquerque EX (1991) Initial characterization of the nicotinic acetylcholine receptors in rat hippocampal neurons. J Receptor Res 11:1001–1022

    CAS  Google Scholar 

  • Alkondon M, Rao KS, Albuquerque EX (1988) Acetylcholinesterase reactivators modify the properties of nicotinic acetylcholine receptor ion channels. J Pharmacol Exp Ther 245:543–556

    PubMed  CAS  Google Scholar 

  • Aracava Y, Ikeda SR, Daly JW, Brookes N, Albuquerque EX (1984) Interactions of bupivacaine with ionic channels of the nicotinic receptor: analysis of single channel currents. Mol Pharmacol 26:304–313

    PubMed  CAS  Google Scholar 

  • Aracava Y, Deshpande SS, Rickett DL, Brossi A, Schönenberger B, Albuquerque EX (1987a) The molecular basis of anticholinesterase actions on nicotinic and glutamatergic synapses. Ann NY Acad Sci 505:226–255

    PubMed  CAS  Google Scholar 

  • Aracava Y, Deshpande SS, Swanson KL, Rapoport H, Wonnacott S, Lunt G, Albuquerque EX (1987b) Nicotinic acetylcholine receptor in cultured neurons from the hippocampus and brain stem of the rat characterized by single channel recording. FEBS Lett 222:63–70

    PubMed  CAS  Google Scholar 

  • Aracava Y, Swanson KL, Rozental R, Albuquerque EX (1988) Structure-activity relationships of (+)anatoxin-a derivatives and? enantiomers of nicotine on the peripheral and central nicotinic acetylcholine receptor subtypes. In: Lunt GG (ed) Neurotox ’88: molecular basis of drug and pesticide action. Elsevier, Cambridge, pp 157–184

    Google Scholar 

  • Aronstam RS, Witkop B (1981) Anatoxin-a interactions with cholinergic synaptic molecules. Proc Natl Acad Sci USA 78:4639–4643

    PubMed  CAS  Google Scholar 

  • Aronstam RS, King CT Jr, Albuquerque EX, Daly JW, Feigl DM (1985) Binding of [3H]perhydrohistrionicotoxin and [3H]phencyclidine to the nicotinic receptor-ion channel complex of Torpedo electroplax. Inhibition by histrionicotoxins and derivatives. Biochem Pharmacol 34:3037–3047

    PubMed  CAS  Google Scholar 

  • Aronstam RS, Daly JW, Spande TF, Narayanan TK, Albuquerque EX (1986) Interaction of gephyrotoxin and indolizidine alkaloids with the nicotinic acetyl-choline receptor-ion channel complex of Torpedo electroplax. Neurochem Res 11:1227–1240

    PubMed  CAS  Google Scholar 

  • Atchison WD, Narahashi T, Vogel SM (1984) Endplate blocking actions of lopho- toxin. Br J Pharmacol 82:667–672

    PubMed  CAS  Google Scholar 

  • Auerbach A, del Castillo J, Specht PC, Titmus M (1983) Correlation of agonist structure with acetylcholine receptor kinetics: studies on the frog end-plate and on chick embryo muscle. J Physiol (Lond.) 343:551–568

    CAS  Google Scholar 

  • Barlow RB, Hamilton JT (1965) The stereospecificity of nicotine. Br J Pharmacol 25:206–212

    CAS  Google Scholar 

  • Barlow RB, McLeod LJ (1969) Some studies on cytisine and its methylated derivatives. Br J Pharmacol 35:161–174

    PubMed  CAS  Google Scholar 

  • Barnard EA, Dolly JO, Porter CW, Albuquerque EX (1975) The acetylcholine receptor and ionic conductance modulation system of skeletal muscle. Exp Neurol 48:1028

    Google Scholar 

  • Barrantes FJ (1978) Agonist-mediated changes of the acetylcholine receptor in its membrane environment. J Mol Biol 124:1–26

    PubMed  CAS  Google Scholar 

  • Barrantes FJ (1980) Modulation of acetylcholine receptor states by thiol modification. Biochemistry 19:2957–2965

    PubMed  CAS  Google Scholar 

  • Beers WH, Reich E (1970) Structure and activity of acetylcholine. Nature 288: 917–922

    Google Scholar 

  • Behling RW, Yamane T, Navon G, Jelinski LW (1988) Conformation of acetylcholine bound to the nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 85:6721–6725

    PubMed  CAS  Google Scholar 

  • Ben-Haim D, Dreyer F, Peper K (1975) Acetylcholine receptor: modification of synaptic gating mechanism after treatment with a disulfide bond reducing agent. Pflugers Arch 355:19–26

    PubMed  CAS  Google Scholar 

  • Bird SJ, Aghajanian JK (1976) The cholinergic pharmacology of hippocampal pyramidal cells: a microiontophoretic study. Neuropharmacology 15:273–282

    PubMed  CAS  Google Scholar 

  • Blaber LC, Bowman WC (1963) The effects of some drugs on the repetitive discharges produced in nerve and muscle by anticholinesterases. Int J Neuropharmacol 2:1–16

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Boksa P, Quirion R (1987) [3H]N-Methyl-carbamylcholine, a new radioligand sepcific for nicotinic acetylcholine receptors in brain. Eur J Pharmacol 139:323–333

    PubMed  CAS  Google Scholar 

  • Bradley PB, Lucy AP (1983) Cholinoceptive properties of respiratory neurones in the rat medulla. Neuropharmacology 22:853–858

    PubMed  CAS  Google Scholar 

  • Brimblecombe RW, Rowsell DG (1969) A comparison of the pharmacological activities of tertiary bases and their quaternary ammonium derivatives. Int J Neuropharmacol 8:131–141

    PubMed  CAS  Google Scholar 

  • Carmichael WM, Biggs DF, Gorham PR (1975) Toxicology and pharmacological action of Anabaena flos-aquae toxin. Science 187:542–544

    PubMed  CAS  Google Scholar 

  • Carmichael WW, Biggs DF, Peterson MA (1979) Pharmacology of anatoxin-a produced by the freshwater cyanophyte Anabaena flos-aquae NRC-44–1. Toxicon 17:229–236

    PubMed  CAS  Google Scholar 

  • Carp JS, Aronstam RS, Witkop B, Albuquerque EX (1983) Electrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics. Proc Natl Acad Sci USA 80:310–314

    PubMed  CAS  Google Scholar 

  • Changeux J-P (1990) Functional architecture and dynamics of the nicotinic acetylcholine receptor: an allosteric ligand-gated ion channel. Fidia Res Found Neurosci Award Lect 4:21–168

    Google Scholar 

  • Clarke PBS (1987) Recent progress in identifying nicotinic cholinoceptors in mammalian brain. TINS 8:32–35

    CAS  Google Scholar 

  • Clarke PBS, Schwartz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]- α-bungarotoxin. J Neurosci 5:1307–1315

    PubMed  CAS  Google Scholar 

  • Collins AC, Evans CB, Miner LL, Marks MJ (1986) Mecamylamine blockade of nicotine responses: evidence for two brain nicotinic receptors. Pharmacol Biochem Behav 24:1767–1773

    PubMed  CAS  Google Scholar 

  • Colquhoun D, Hawkes AG (1983) The principles of the stochastic interpretation of ion-channel mechanisms. In: Sakmann B, Neher E (eds) Single-channel recording. Plenum, New York, pp 135–175

    Google Scholar 

  • Colquhoun D, Rang JP (1976) Effects of inhibitors on the binding of iodinated α-bungarotoxin to acetylcholine receptors in rat muscle. Mol Pharmacol 12: 519–535

    PubMed  CAS  Google Scholar 

  • Connolly JG (1989) Structure-function relationships in nicotinic acetylcholine receptors. Comp Biochem Physiol [A] 93:221–231

    CAS  Google Scholar 

  • Contreras PC, Rafferty MF, Lessor RA, Rice KC, Jacobson AE, O’Donohue TL (1985) A specific alkylating ligand for phencyclidine (PCP) receptors antagonizes PCP behavioral effects. Eur J Pharmacol 111:405–406

    PubMed  CAS  Google Scholar 

  • Cooper E (1990) Evidence that functional neuronal nicotinic AChRs have pentameric structures. Soc Neurosci Abstr 16:10

    Google Scholar 

  • Costa ACS, Swanson KL, Aracava Y, Aronstam RS, Albuquerque EX (1990) Molecular effects of dimethylanatoxin on the peripheral nicotinic acetylcholine receptor. J Pharmacol Exp Ther 252:507–516

    PubMed  CAS  Google Scholar 

  • Culver P, Jacobs RS (1981) Lophotoxin: a neuromuscular acting toxin from the sea whip (Lophorgorgia rigida). Toxicon 19:825–830

    PubMed  CAS  Google Scholar 

  • Culver P, Fenical W, Taylor P (1984) Lophotoxin irreversibly inactivates the nicotinic acetylcholine receptor by preferential association at one of the two primary agonist sites. J Biol Chem 259:3763–3770

    PubMed  CAS  Google Scholar 

  • Culver P, Burch M, Potenza C, Wasserman L, Fenical W, Taylor P (1985) Structure- activity relationships for the irreversible blockade of nicotinic receptor agonist sites by lophotoxin and congeneric diterpene lactones. Mol Pharmacol 28:436–444

    PubMed  CAS  Google Scholar 

  • Cuns JCT, Aracava Y, Albuquerque EX (1990) Atropine actions on nicotinic receptors: single channel analysis. Biophys J 57:123a

    Google Scholar 

  • Dale HH (1914) The action of certain esters and ethers of choline, and their relation to muscarine. J Pharmacol Exp Ther 6:147–190

    CAS  Google Scholar 

  • Dani JA (1989) Open channel structure and ion binding sites of the nicotinic acetylcholine receptor channel. J Neurosci 9:884–892

    PubMed  CAS  Google Scholar 

  • Deguchi R, Narahashi T, Haas HG (1971) Mode of action of nereistoxin on the neuromuscular transmission in the frog. Pestic Biochem Physiol 1:196–204

    CAS  Google Scholar 

  • Del Castillo J, Katz B (1957) Interaction at end-plate receptors between different choline derivatives. Proc R Soc Lond 146:369–381

    Google Scholar 

  • Deshpande SS, Viana GB, Kauffman FC, Rickett DL, Albuquerque EX (1986) Effectiveness of physostigmine as a pretreatment drug for protection of rats from organophosphate poisoning. Fundam Appl Toxicol 6:566–577

    PubMed  CAS  Google Scholar 

  • Ehlert FJ, Jenden DJ (1984) Comparison of the muscarinic receptor binding activity of some tertiary amines and their quaternary ammonium analogues. Mol Pharmacol 25:46–50

    PubMed  CAS  Google Scholar 

  • Eldefrawi A, Bakry NM, Eldefrawi NE, Tsai M-C, Albuquerque EX (1980) Nereistoxin interaction with the acetylcholine receptor-ionic channel complex. Mol Pharmacol 17:172–179

    PubMed  CAS  Google Scholar 

  • Feltz A, Trautmann A (1982) Desensitization at the frog neuromuscular junction: a biphasic process. J Physiol (Lond) 322:257–272

    CAS  Google Scholar 

  • Fenical W, Okuda RK, Bandurraga MM, Culver P, Jacobs RS (1981) Lophotoxin: a novel neuromuscular toxin from pacific sea whips of the genus Lophogorgia. Science 212:1512–1514

    PubMed  CAS  Google Scholar 

  • Fertuck HC, Salpeter MM (1974) Localization of acetylcholine receptor by 125I- labeled α-bungartoxin binding at mouse motor endplates. Proc Nat Acad Sci USA 71:1376–1378

    PubMed  CAS  Google Scholar 

  • Fiekers JF, Spannbauer PM, Scubon-Mulieri B, Parsons RL (1980) Voltage dependence of desensitization: influence of calcium and activation kinetics. J Gen Physiol 75:511–529

    PubMed  CAS  Google Scholar 

  • French ED, Jacobson AE, Rice KC (1987) Metaphit, a proposed phencyclidine (PCP) antagonist, prevents PCP-induced locomotor behavior through mechanisms unrelated to specific blockade of PCP receptors. Eur J Pharmacol 140:267–274

    PubMed  CAS  Google Scholar 

  • Fróes-Ferrão MM, Rozental R, Albuquerque EX (1991) Single channel currents activated by physostigmine at junctional nicotinic acetylcholine receptor of mammalian and amphibian. Soc Neurosci Abs 17:751

    Google Scholar 

  • Gage PW, Hamill OP, Wachtel RE (1983) Sites of action of procaine at the motor end-plate. J Physiol (Lond) 335:123–137

    CAS  Google Scholar 

  • Giblin BA, Lumpkin MD, Kellar KJ (1988) Repeated administration of nicotine results in long-term decrease in prolactin release by acute nicotine in rats. Soc Neurosci Abstr 14:1328

    Google Scholar 

  • Giraudat J, Dennis M, Heidmann T, Haumont P-Y, Lederer F, Changeux J-P (1987) Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the ß and γ chains. Biochemistry 26:4210–4218

    Google Scholar 

  • Giraudat J, Galzi J-L, Revah F, Changeux J-P, Haumont P-Y, Lederer F (1989) The noncompetitive blocker [3H]chlorpromazine labels segment M2 but not segment Ml of the nicotinic acetylcholine receptor a-subunit. FEBS Lett 253:190–198

    PubMed  CAS  Google Scholar 

  • Grenningloh G, Reinitz A, Schmitt C, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H (1987) The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 328:215–220

    PubMed  CAS  Google Scholar 

  • Hanin I, Jenden DJ, Cho AK (1966) The influence of pH on the muscarinic action of oxotremorine, arecoline, pilocarpine, and their quaternary ammonium analogs, Mol Pharmacol 2:352–359

    PubMed  CAS  Google Scholar 

  • Hayashi E, Yamada S (1975) Pharmacological studies on surugatoxin, the toxic principle from Japanese ivory mollusc (Babylonia japonica). Br J Pharmacol 53:206–215

    Google Scholar 

  • Hey P (1952) On relationships between structure and nicotine-like stimulant activity in choline esters and ethers. Br J Pharmacol 7:117–129

    CAS  Google Scholar 

  • Hubbard JI, Schmidt RF, Yokota T (1965) The effect of acetycholine upon mammalian motor nerve terminals. J Physiol (Lond) 181:810–829

    CAS  Google Scholar 

  • Hucho F (1986) The nicotinic acetylcholine receptor and its ion channel. Eur J Biochem 158:211–226

    PubMed  CAS  Google Scholar 

  • Hucho FL, Oberthür W, 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

    PubMed  CAS  Google Scholar 

  • Huganir RL, Delcour AH, Greengard P, Hess GP (1986) Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature 321:744–776

    Google Scholar 

  • Huganir RL, Greengard P (1987) Regulation of receptor function by protein phosphorylation. Trends Pharmacol Sci 8:472–477

    CAS  Google Scholar 

  • Idriss MK, Aguayo LG, Rickett D, Albuquerque EX (1986) Organophosphate and carbamate compounds have pre- and postjunctional effects at the insect glutamatergic synapse. J Pharmacol Exp Ther 239:279–285

    PubMed  CAS  Google Scholar 

  • Ikeda SR, Aronstam RS, Daly JW, Aracava Y, Albuquerque EX (1984) Interactions of bupivacaine with ionic channels of the nicotinic receptor: electrophysiological and biochemical studies. Mol Pharmacol 26:293–303

    PubMed  CAS  Google Scholar 

  • Jennings KR, Brown DG, Wright DP Jr (1986) Methyllycaconitine, a naturally occurring insecticide with a high affinity for the insect cholinergic receptor. Experentia 42:611–613

    CAS  Google Scholar 

  • Kanne DB, Abood LG (1988) Synthesis and biological characterization of pyrido- homotropanes. Structure-activity relationships of conformationally restricted nicotinoids. J Med Chem 31:506–509

    PubMed  CAS  Google Scholar 

  • Karlin A (1969) Chemical modification of the active site of the acetylcholine receptor. J Gen Physiol 54:245s–264s

    CAS  Google Scholar 

  • Karlin A (1980) Molecular properties of nicotinic acetylcholine receptors In: Cotman CW, Poste G, Nicolson GL (eds) The Cell Surface and Neuronal Function. Elsevier Amsterdam, pp 191–206

    Google Scholar 

  • Karlin A (1983) The anatomy of a receptor. Neuroscience Commentaries 1:111–123

    Google Scholar 

  • Karpen JW, Hess GP (1986a) Cocaine, phencyclidine, and procaine inhibition of the acetylcholine receptor: characterization of the binding site by stopped-flow measurements of receptor-controlled ion flux in membrane vesicles. Biochemistry 25:1777–1785

    PubMed  CAS  Google Scholar 

  • Karpen JW, Hess GP (1986b) Acetylcholine inhibition by D-tubocurarine involves both a competitive and a noncompetitive binding site as determined by stopped- flow measurements of receptor-controlled ion flux in membrane vesicles. Biochemistry 25:1786–1792

    PubMed  CAS  Google Scholar 

  • Katz B, Miledi R (1978) A re-examination of curare action at the motor endplate. Proc R Soc Lond [Biol] 203:119–133

    CAS  Google Scholar 

  • Kawabuchi M, Boyne AF, Deshpande SS, Cintra WM, Brossi S, Albuquerque EX (1988) Enantiomer (-h)physostigmine prevents organophosphate-induced sub- junctional damage at the neuromuscular synapse by a mechanism not related to Cholinesterase carbamylation. Synapse 2:139–147

    PubMed  CAS  Google Scholar 

  • Kellar KJ, Wonnacott S (1990) Nicotinic cholinergic receptors in Alzheimer’s disease. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology. Oxford University Press, Oxford, pp 341–373

    Google Scholar 

  • Knappe U, Wirtz-Brugger F, Cornfeldt M, Fielding S (1988) Effects of hemicholinium-3 on brainstem auditory evoked potentials in the rat. Soc Neurosci Abstr 14:800

    Google Scholar 

  • Kosuge T, Tsuji K, Hirai K (1982) Isolation of neosurugatoxin from the Japanese ivory shell, Babylonia japonica. Chem Pharm Bull (Tokyo) 9:3255–3259

    Google Scholar 

  • Kuba K, Albuquerque EX, Barnard EA (1973) Diisopropylfluorophosphate: suppression of ionic conductance of the cholinergic receptor. Science 181: 853–856

    PubMed  CAS  Google Scholar 

  • Kuba K, Albuquerque EX, Daly J, Barnard EA (1974) A study of the irreversible Cholinesterase inhibitor, diisopropylfluorophosphate, on time course of endplate currents in frog sartorius muscle. J Pharmacol Exp Ther 189:499–512

    PubMed  CAS  Google Scholar 

  • Kuhlmann J, Okonjo KO, Maelicke A (1991) Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel. FEBS Lett 279:216–218

    PubMed  CAS  Google Scholar 

  • Lambert JJ, Voile RL, Henderson EG (1980) An attempt to distinguish between the actions of neuromuscular blocking drugs on the acetylcholine receptor and on its associated ionic channel. Proc Natl Acad Sci USA 77:5003–5007

    PubMed  CAS  Google Scholar 

  • Langdon RB, Jacobs RS (1985) Irreversible autonomic actions by lophotoxin suggest utility as a probe for both C6 and CIO nicotinic receptors. Brain Res 359:233–238

    PubMed  CAS  Google Scholar 

  • Langley JN (1905) On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J Physiol (Lond) 33:374–413

    Google Scholar 

  • Laskowski MB, Dettbarn W-D (1975) Presynaptic effects of neuromuscular Cholinesterase inhibition. J Pharmacol Exp Ther 194:351–361

    PubMed  CAS  Google Scholar 

  • Lauffer L, Hucho F (1982) Triphenylmethylphosphonium is an ion channel ligand of the nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 79:2406–2409

    PubMed  CAS  Google Scholar 

  • Leprince P (1983) Chemical modification of the nicotinic cholinergic receptor of PC-12 nerve cell. Biochemistry 22:5551–5556

    PubMed  CAS  Google Scholar 

  • Lima-Landman MT, Albuquerque EX (1988) The novel neurotoxin H12- histrionicotoxin blocks the N-methyl-D-aspartate receptor of cultured hippocampus of the rat. Soc Neurosci Abstr 14:96

    Google Scholar 

  • Lipton SA, Aizeman E, Loring RH (1987) Neural nicotinic acetylcholine responses in solitary mammalian retinal ganglion cell. Pflugers Arch 410:37–43

    PubMed  CAS  Google Scholar 

  • London ED, Ball MJ, Waller SB (1989) Nicotinic binding sites in cerebral cortex and hippocampus in Alzheimer’s dementia. Neurochem Res 14:745–750

    PubMed  CAS  Google Scholar 

  • Luetje CW, Patrick J (1991) Both alpha and beta subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. J Neurosci 11:837–845

    PubMed  CAS  Google Scholar 

  • Luetje CW, Wada K, Rogers S, Abramson SN, Tsuji K, Heinemann S, Patrick J (1990) Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations. J Neurochem 55:632–640

    PubMed  CAS  Google Scholar 

  • MacAllan DRE, Lunt GG, Wonnacott S, Swanson KL, Rapoport H, Albuquerque EX (1988) Methyllycaconitine and (+)anatoxin-a differentiate between nicotinic receptors in vertebrate and invertebrate nervous systems. FEBS Lett 226:357–363

    PubMed  CAS  Google Scholar 

  • Madsen BW, Albuquerque EX (1985) The narcotic antagonist naltrexone has a biphasic effect on the nicotinic acetylcholine receptor. FEBS Lett 182:20–24

    PubMed  CAS  Google Scholar 

  • Magleby KL, Stevens CF (1972) A quantitative description of end-plate currents. J Physiol (Lond.) 223:173–197

    CAS  Google Scholar 

  • Maleque MA, Takahashi K, Witkop B, Brossi A, Albuquerque EX (1984) A study of the novel synthetic analog (±)-depentylperhydrohistrionicotoxin on the nicotinic receptor-ion channel. J Pharmacol Exp Ther 230:619–626

    PubMed  CAS  Google Scholar 

  • Manalis RS (1977) Voltage-dependent effect of curare at the frog neuromuscular junction. Nature 267:366–367

    PubMed  CAS  Google Scholar 

  • Masukawa LM, Albuquerque EX (1978) Voltage- and time-dependent action of histrionicotoxin on the endplate current of the frog muscle. J Gen Physiol 72:351–367

    PubMed  CAS  Google Scholar 

  • Meyerhoff JL, Bates VE (1985) Combined treatment with muscarinic and nicotinic cholinergic antagonists slows development of kindled seizures. Brain Res 339:386–389

    PubMed  CAS  Google Scholar 

  • Middleton P, Jamarillo F, Schuetze SM (1986) Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates. Proc Natl Acad Sci USA 83:4967–4971

    PubMed  CAS  Google Scholar 

  • Milne RJ, Byrne JH (1981) Effects of hexamethonium and decamethonium on end-plate current parameters. Mol Pharmacol 19:276–281

    PubMed  CAS  Google Scholar 

  • Miner LL, Marks MJ, Collins AC (1986) Genetic analysis of nicotine-induced seizures and hippocampal nicotinic receptors in the mouse. J Pharmacol Exp Ther 239:853–860

    PubMed  CAS  Google Scholar 

  • Monod J, Wyman J, Changeux J-P (1965) On the nature of allosteric Transltions: a plausible model. J Mol Biol 12:88–118

    PubMed  CAS  Google Scholar 

  • Nambi Aiyar V, Benn MH, Hanna T, Jacyno J, Roth SH, Wilkens JL (1979) The principal toxin of Delphinium brownii Rydb. and its mode of action. Experentia 35:1367–1368

    Google Scholar 

  • Nastuk WL, Parsons RL (1970) Factors in the inactivation of postjunctional membrane receptors of frog skeletal muscle. J Gen Physiol 56:218–249

    PubMed  CAS  Google Scholar 

  • Neher E (1983) The charge carried by single channel currents of rat cultured muscle cells in the presence of local anesthetics. J Physiol (Lond) 339:663–678

    CAS  Google Scholar 

  • Neher E, Steinbach JH (1978) Local anaesthetics Translently block currents through single acetylcholine-receptor channels. J Physiol (Lond) 277:173–176

    Google Scholar 

  • Nilsson L, Adem A, Hardy J, Winblad B, Nordberg A (1987) Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors? j Neural Transm 70:357–368

    PubMed  CAS  Google Scholar 

  • Oberthür W, Muhn P, Baumann H, Lottspeich F, Wittmann-Liebold B, Hucho F (1986) The reaction site of a non-competitive antagonist in the δ-subunit of the nicotinic acetylcholine receptor. EMBO J 5:1815–1519

    PubMed  Google Scholar 

  • Ochoa ELM, Chattopadhyay A, McNamee MG (1989) Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cell Mol Neurobiol 9:141–178

    PubMed  CAS  Google Scholar 

  • Okonjo KO, Kuhlmann J, Maelicke A (1991) A second pathway of activation of the nicotinic acetylcholine receptor ion channel. Eur J Biochem 200:671–677

    PubMed  CAS  Google Scholar 

  • Oliveira L, Madsen BW, Kapai N, Sherby SM, Swanson KL, Eldefrawi ME, Albuquerque EX (1987) Interaction of narcotic antagonist naltrexone with nicotinic acetylcholine receptor. Eur J Pharmacol 140:331–342

    PubMed  CAS  Google Scholar 

  • Pabreza LA, Dhawan S, Kellar K (1991) [3H]Cytisine binding to nicotinic cholinergic receptors in brain. Mol Pharmacol 39:9–12

    PubMed  CAS  Google Scholar 

  • Papke RL, Millhauser G, Lieberman Z, Oswald RE (1988) Relationships of agonist properties to the single channel kinetics of nicotinic acetylcholine receptors. Biophys J 53:1–10

    PubMed  CAS  Google Scholar 

  • Parkinson D, Kratz KE, Daw NW (1988) Evidence for a nicotinic component to the actions of acetylcholine in cat visual cortex. Exp Brain Res 73:553–568

    PubMed  CAS  Google Scholar 

  • Pascuzzo GJ, Akaike A, Maleque MA, Shaw K-P, Aronstam RS, Rickett DL, Albuquerque EX (1984) The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing and binding properties. Mol Pharmacol 25:92–101

    PubMed  CAS  Google Scholar 

  • Paton WDM, Zaimis EJ (1952) The methonium compounds. Pharmacol Rev 4:219–253

    PubMed  CAS  Google Scholar 

  • Pedersen SE, Cohen JB (1990) D-Tubocurarine 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

    PubMed  CAS  Google Scholar 

  • Pereira EFR, Wonnacott S, Albuquerque EX (1991a) Methyllycaconitine is a potent antagonist of nicotinic acetylcholine receptors on rat hippocampal neurons: single channel studies. Soc Neurosci Abs 17:960

    Google Scholar 

  • Pereira EFR, Alkondon M, Albuquerque EX (1991b) Effects of organophosphate (OP) compounds and physostigmine (PHY) on nicotinic acetylcholine receptors (AChR) in the mammalian central nervous system (CNS). Proceedings of the 1991 Medical Defense Bioscience Review. US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD. pp 229–233

    Google Scholar 

  • Peterson GL (1989) Consensus residues at the acetylcholine binding site of cholinergic proteins. J Neurosci Res 22:488–503

    PubMed  CAS  Google Scholar 

  • Ramoa AS, Albuquerque EX (1988) Phencyclidine and some of its analogues have distinct effects on NMDA receptors of rat hippocampal neurons. FEBS Lett 235:156–162

    PubMed  CAS  Google Scholar 

  • Ramoa AS, Alkondon M, Aracava Y, Irons J, Lunt GG, Deshpande SS, Wonnacott S, Aronstam RS, Albuquerque EX (1990) The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels. J Pharmacol Exp Ther 254:71–82

    PubMed  CAS  Google Scholar 

  • Rang HP, Ritter JM (1969) The relationship between desensitization and the metaphilic effect at cholinergic receptors. Mol Pharmacol 6:383–390

    Google Scholar 

  • Rang HP, Ritter JM (1971) The effect of disulfide bond reduction on the properties of cholinergic receptors in chick muscle. Mol Pharmacol 7:620–631

    PubMed  CAS  Google Scholar 

  • Rao KS, Aracava Y, Rickett DL, Albuquerque EX (1987) Noncompetitive blockade of the nicotinic acetylcholine receptor-ion channel complex by an irreversible Cholinesterase inhibitor. J Pharmacol Exp Ther 240:337–344

    PubMed  CAS  Google Scholar 

  • Rapier C, Wonnacott S, Lunt GG, Albuquerque EX (1987) The neurotoxin histrionicotoxin interacts with the putative ion channel of the nicotinic acetylcholine receptors in the central nervous system. FEBS Lett 212:292–296

    PubMed  CAS  Google Scholar 

  • Rapier C, Lunt GG, Wonnacott S (1988) Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetitive stimulation. J Neurochem 50:1123–1130

    PubMed  CAS  Google Scholar 

  • Rapier C, Lunt GG, Wonnacott S (1990) Nicotinic modulation of [3H]dopamine release from striatal synaptosomes: pharmacological characterisation. J Neurochem 54:937–945

    PubMed  CAS  Google Scholar 

  • Reddy VK, Deshpande SS, Cintra WM, Scoble GT, Albuquerque EX (1991) Effectiveness of oximes 2-PAM and HI-6 in recovery of muscle function depressed by organophosphate agents in the rat hemidiaphragm: an in vitro study. Fundam Appl Toxicol 17:746–760

    PubMed  CAS  Google Scholar 

  • Roberts F, Lazareno S (1989) Cholinergic treatments for Alzheimer’s disease. Biochem Soc Trans 17:76–79

    PubMed  CAS  Google Scholar 

  • Romano C, Goldstein A (1980) Stereospecific nicotine receptors on rat brain membranes. Science 210:647–650

    PubMed  CAS  Google Scholar 

  • Rovira C, Ben-Ari Y, Cherubini E, Krnjevic K, Roper N (1983) Pharmacology of the dendritic action of acetylcholine and further observations on the somatic disinhibition in the rat hippocampus in situ. Neuroscience 8:97–106

    PubMed  CAS  Google Scholar 

  • Rozental R, Aracava Y, Scoble GT, Swanson KL, Wonnacott S, Albuquerque EX (1989) The agonist recognition site of the peripheral acetylcholine receptor ion channel complex differentiates the enantiomers of nicotine. J Pharmacol Exp Ther 251:395–404

    PubMed  CAS  Google Scholar 

  • Sanchez JA, Dani JA, Siemen D, Hille B (1986) Slow permeation of organic cations in acetylcholine receptor channels. J Gen Physiol 87:985–1001

    PubMed  CAS  Google Scholar 

  • Schofield GG, Warnick JE, Albuquerque EX (1981) Elucidation of the mechanism and site of action of quinuclidinyl benzilate (QNB) on the electrical excitability and chemosensitivity of the frog sartorius muscle. Cell Mol Neurobiol 1:209–230

    PubMed  CAS  Google Scholar 

  • Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA (1987) Sequence and functional expression of the GABAa receptor shows a ligand-gated receptor super-family. Nature 328:221–227

    PubMed  CAS  Google Scholar 

  • Schwartz RD, Mindlin MC (1988) Inhibition of the GABA receptor-gated ion channel in brain by noncompetitive inhibitors of the nicotinic receptor-gated cation channel. J Pharmacol Exp Ther 244:963–970

    PubMed  CAS  Google Scholar 

  • Shaker N, Eldefrawi AT, Aguayo LG, Warnick JE, Albuquerque EX, Eldefrawi ME (1982) Interactions of D-tubocurarine with the nicotinic acetylcholine receptor/ channel molecule. J Pharmacol Exp Ther 220:172–177

    PubMed  CAS  Google Scholar 

  • Shaw K-P, Aracava Y, Akaike A, Daly JW, Rickett DL, Albuquerque EX (1985) The reversible Cholinesterase inhibitor physostigmine has channel-blocking and agonist effects on the acetylcholine receptor-ion channel complex. Mol Pharmacol 28:527–538

    PubMed  CAS  Google Scholar 

  • Sherby SM, Eldefrawi AT, Albuquerque EX, Eldefrawi ME (1985) Comparison of the actions of carbamate anticholinesterases on the nicotinic acetylcholine receptor. Mol Pharmacol 27:343–348

    PubMed  CAS  Google Scholar 

  • Sheridan RP, Nilakantan R, Dixon JS, Venkataraghavan R (1986) The ensemble approach to distance geometry: application to the nicotinic pharmacophore. J Med Chem 29:899–906

    PubMed  CAS  Google Scholar 

  • Sine SM, Steinbach JH (1986) Acetylcholine receptor activation by a site-selective ligand: nature of brief open and closed states in BC3H-1 cells. J Physiol (Lond) 370:357–379

    CAS  Google Scholar 

  • Sine SM, Taylor P (1981) Relationship between reversible antagonist occupancy and the functional capacity of the acetylcholine receptor. J Biol Chem 256:6692–6699

    PubMed  CAS  Google Scholar 

  • Siren A-L, Feuerstein G (1990) Cardiovascular effects of AnTX-a in the conscious rat. Toxicol Appl Pharmacol 102:91–100

    PubMed  CAS  Google Scholar 

  • Skok VI, Selyanko AA, Derkach BA (1989) Neuronal acetylcholine receptors. Plenum, New York

    Google Scholar 

  • Sorenson EM, Culver P, Chiappinelli VA (1987) Lophotoxin: selective blockade of nicotinic transmission in autonomic ganglia by a coral neurotoxin. Neuroscience 20:875–884

    PubMed  CAS  Google Scholar 

  • Spivak CE, Albuquerque EX (1982) Dynamic properties of the nicotinic acetylcholine receptor ionic channel complex: activation and blockade. In: Hanin I, Goldberg AM (eds) Progress in cholinergic biology: model cholinergic synapses. Raven, New York, pp 323–357

    Google Scholar 

  • Spivak CE, Albuquerque EX (1985) Triphenylmethylphosphonium blocks the nicotinic acetylcholine receptor noncompetitively. Mol Pharmacol 27:246–255

    PubMed  CAS  Google Scholar 

  • Spivak CE, Witkop B, Albuquerque EX (1980) Anatoxin-a: a novel, potent agonist at the nicotinic receptor. Mol Pharmacol 18:384–394

    PubMed  CAS  Google Scholar 

  • Spivak CE, Maleque MA, Oliveira AC, Masukawa LM, Tokuyama T, Daly JW, Albuquerque EX (1982) Actions of histrionicotoxins at the ion channel of the nicotinic acetylcholine receptor and at the voltage-sensitive ion channels of muscle membranes. Mol Pharmacol 21:351–361

    PubMed  CAS  Google Scholar 

  • Spivak CE, Maleque MA, Takahashi K, Brossi A, Albuquerque EX (1983a) The ionic channel of the nicotinic acetylcholine receptor is unable to differentiate between the optical antipodes of perhydrohistrionicotoxin. FEBS Lett 163:189–193

    PubMed  CAS  Google Scholar 

  • Spivak CE, Waters J, Witkop B, Albuquerque EX (1983b) Potencies and channel properties induced by semirigid agonists at frog nicotinic acetylcholine receptors. Mol Pharmacol 23:337–343

    PubMed  CAS  Google Scholar 

  • Steinbach AB (1968) Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end-plate potential. J Gen Physiol 52:144–161

    PubMed  CAS  Google Scholar 

  • Steinbach JH, Zemple J (1987) What does phosphorylation do for the nicotinic acetylcholine receptor. Trends Neurosci 10:61–64

    CAS  Google Scholar 

  • Stitzel JA, Campbell SM, Collins AC, Marks MJ (1988) Sulfhydryl modification of two nicotinic binding sites in mouse brain. J Neurochem 50:920–928

    PubMed  CAS  Google Scholar 

  • Stroud RM (1980) Acetylcholine receptor structure In: Cotman CW, Poste G, Nicolson GL (eds) The Cell Surface and Neuronal Function. Elsevier/North- Holland Biomedical Press, pp 124–138

    Google Scholar 

  • Swanson KL, Albuquerque EX (1987) Nicotinic acetylcholine receptor ion channel blockade by cocaine: the mechanism of synatpic action. J Pharmacol Exp Ther 243:1202–1210

    PubMed  CAS  Google Scholar 

  • Swanson KL, Allen CN, Aronstam RS, Rapoport H, Albuquerque EX (1986) Molecular mechanisms of the potent and stereospecific nicotinic receptor agonist (+)-anatoxin-a. Mol Pharmacol 29:250–257

    PubMed  CAS  Google Scholar 

  • Swanson KL, Aracava Y, Sardina FJ, Aronstam RS, Rapoport H, Albuquerque EX (1989) N-methylanatoxinol isomers: derivatives of the agonist anatoxin-a block the nicotinic acetylcholine receptor ion channel. Mol Pharmacol 35:223–231

    PubMed  CAS  Google Scholar 

  • Swanson KL, Rapoport H, Aronstam RS, Albuquerque EX (1990) Nicotinic acetylcholine receptor function studied with synthetic (+)-anatoxin-a and derivatives. ACS Symp Ser 418:107–118

    CAS  Google Scholar 

  • Swanson KL, Aronstam RS, Wonnacott S, Rapoport H, Albuquerque EX (1991) Nicotinic pharmacology of anatoxin analogs. I. Side chain structure-activity relationships at peripheral agonist and noncompetitive antagonist sites. J Pharmacol Exp Therap 259:377–386

    CAS  Google Scholar 

  • Tano T, Rice K, Aronstam RS, Oliveira AC, Aracava Y, Albuquerque EX (1990) Effect of metaphit on the peripheral nicotinic acetylcholine receptor. Soc Neurosci Abstr 16:207

    Google Scholar 

  • Terrar DA (1978) Effects of dithiothreitol on end-plate currents. J Physiol (Lond) 26:403–417

    Google Scholar 

  • Tiedt TN, Albuquerque EX, Bakry NM, Eldefrawi ME, Eldefrawi AT (1979) Voltage- and time-dependent actions of piperocaine on the ion channel of the acetylcholine receptor. Mol Pharmacol 16:909–921

    PubMed  CAS  Google Scholar 

  • Triggle DJ, Triggle CR (1976) Chemical pharmacology of the synapse. Academic, London

    Google Scholar 

  • Tsai M-C, Mansour NA, Eldefrawi AT, Eldefrawi ME, Albuquerque EX (1978) Mechanism of action of amantadine on nepromuscular transmission. Mol. Pharmacol 14:787–803

    CAS  Google Scholar 

  • Tsai M-C, Oliveira AC, Albuquerque EX, Eldefrawi ME, Eldefrawi AT (1979) Mode of action of quinacrine on the acetylcholine receptor ionic channel complex. Mol Pharmacol 16:382–392

    PubMed  CAS  Google Scholar 

  • Unna K, Kniazuk M, Greslin JG (1944) Pharmacologic action of Erythrina alkaloids. I. ß-erythroidine and substances derived from it. J Pharmacol 80:39–53

    CAS  Google Scholar 

  • Vidal C, 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

    PubMed  CAS  Google Scholar 

  • Wada A, Uezono Y, Arita M, Tsuji K, Yanagihara N, Kobayashi H, Izumi F (1989) High-affinity and selectivity of neosurugatoxin for the inhibition of 22Na influx via nicotinic receptor-ion channel in cultured bovine adrenal medullary cells: comparative study with histrionicotoxin. Neuroscience 33:333–339

    PubMed  CAS  Google Scholar 

  • Wang CM, Narahashi T (1972) Mechanisms of dual action of nicotine on end-plate membranes. J Pharmacol Exp Ther 182:427–441

    PubMed  CAS  Google Scholar 

  • Ward JM, Cockcroft VB, Lunt GG, Smillie FS, Wonnacott S (1990) Methyl- lycaconitine: a selective probe for neuronal abungarotoxin binding sites. FEBS Lett 270:45–48

    PubMed  CAS  Google Scholar 

  • Warnick JE, Aguayo LG, Maleque MA, Albuquerque EX (1982a) N-Alkyl analogs of phencyclidine on twitch and endplate currents. Fed Proc 41:1333

    Google Scholar 

  • Warnick JE, Jessup PS, Overman LE, Eldefrawi ME, Nimit Y, Daly JW, Albuquerque JW (1982b) Pumiliotoxin-C and synthetic analogues. A new class of nicotinic antagonists. Mol Pharmacol 22:565–573

    PubMed  CAS  Google Scholar 

  • Warnick JE, Maleque MA, Bakry N, Eldefrawi AT, Albuquerque EX (1982c) Structure-activity relationships of amantadine. I. Interaction of the N-alkyl analogues with the ionic channels of the nicotinic acetylcholine receptor and electrically excitable membrane. Mol Pharmacol 22:82–93

    PubMed  CAS  Google Scholar 

  • Warnick JE, Maleque MA, Albuquerque EX (1984) Interaction of bicyclo-octane analogs of amantadine with ionic channels of the nicotinic acetylcholine receptor and electrically excitable membrane. J Pharmacol Exp Ther 228:73–79

    PubMed  CAS  Google Scholar 

  • Waters JA, Spivak CE, Hermsmeier M, Yadav JS, Liang RF, Gund TM (1988) Synthesis, pharmacology, and molecular modeling studies of semirigid, nicotinic agonists. J Med Chem 31:545–554

    PubMed  CAS  Google Scholar 

  • Wessler I (1989) Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors. TIPS 10:110–114

    PubMed  CAS  Google Scholar 

  • Whitehouse PJ, Martino AM, Antuono PH, Lowenstein PR, Coyle JT, Price DL, Kellar KJ (1986) Nicotinic acetylcholine binding sites in Alzheimer’s disease. Brain Res 371:146–151

    PubMed  CAS  Google Scholar 

  • Whiting P, Esch F, Shimasake S, Lindstrom J (1987) Neuronal nicotinic acetylcholine receptor β-subunit is coded for by the cDNA clone α4. FEBS Lett 219:459–464

    PubMed  CAS  Google Scholar 

  • Williams H, Robinson JL (1984) Binding of the nicotinic cholinergic antagonist, dihydro-β-erythroidine, to rat brain tissue. J Neurosci 4:2906–2911

    PubMed  CAS  Google Scholar 

  • Woodhull AM (1973) Ionic blockage of sodium channels in nerve. J Gen Physiol 61:687–708

    PubMed  CAS  Google Scholar 

  • Wonnacott S (1986) α-Bungarotoxin binds to low-affinity nicotine binding sites in rat brain. J Neurochem 47:1706–1712

    PubMed  CAS  Google Scholar 

  • Wonnacott S, Jackman S, Swanson KL, Rapoport H, Albuquerque EX (1991) Nicotinic pharmacology of anatoxin analogs. II. Side chain structure-activity relationships at neuronal nicotinic ligand binding sites. J Pharmacol Exp Therap 259:387–391

    CAS  Google Scholar 

  • Wonnacott S, Swanson KL, Albuquerque EX, Huby NJS, Thompson P, Gallagher, T. Honoanatoxin: a potent analogue of anatoxin-a. Biochem Pharmacol (in press)

    Google Scholar 

  • Wright PG (1954) An analysis of the central and peripheral components of respiratory failure produced by anticholinesterase poisoning in the rabbit. J Physiol (Lond.) 126:52–70

    CAS  Google Scholar 

  • Yamada S, Iosgai M, Magawa Y, Takayanagi N, Hayashi E, Tsuji K, Kosuge T (1985) Brain nicotinic acetylcholine receptors: biochemical characterization by neosurugatoxin. Mol Pharmacol 28:120–127

    PubMed  CAS  Google Scholar 

  • Yamada S, Kagawa Y, Takayangi N, Nakayama K, Tsuji K, Kosuge T, Hayashi E, Okada K, Inoue S (1987) Comparison of antinicotinic activity by neosurugatoxin and the structurally related compounds. J Pharmacol Exp Ther 243:1153–1158

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. K. L. Swanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. X. Albuquerque
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Pharmakologie, Freien Universität, Thielallee 69/73, 14195, Berlin, Germany

    Hans Herken

  2. Institut für Biochemie, Freien Universität, Thielallee 63, 14195, Berlin, Germany

    Ferdinand Hucho

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Swanson, K.L., Albuquerque, E.X. (1994). Nicotinic Acetylcholine Receptors and Low Molecular Weight Toxins. In: Herken, H., Hucho, F. (eds) Selective Neurotoxicity. Springer Study Edition, vol 102. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85117-9_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-85117-9_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-57815-4

  • Online ISBN: 978-3-642-85117-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation