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Receptor-mediated presynaptic facilitation of quantal release of acetylcholine induced by pralidoxime inAplysia

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Summary

  1. 1.

    Possible interactions of contrathion (pralidoxime sulfomethylate), a reactivator of phosphorylated acetylcholinesterase (AChE), with the regulation of cholinergic transmission were investigated on an identified synapse in the buccal ganglion ofAplysia californica.

  2. 2.

    Transmitter release was evoked either by a presynaptic action potential or, under voltage clamp, by a long depolarization of the presynaptic cell. At concentrations higher than 10−5 M, bath-applied contrathion decreased the amplitude of miniature postsynaptic currents and increased their decay time. At the same time, the quantal release of ACh was transiently facilitated. The facilitatory effect of contrathion was prevented by tubocurarine but not by atropine. Because in this preparation, these drugs block, respectively, the presynaptic nicotinic-like and muscarinic-like receptors involved in positive and negative feedback of ACh release, we proposed that contrathion activates presynaptic nicotinic-like receptors.

  3. 3.

    Differential desensitization of the presynaptic receptors is proposed to explain the transience of the facilitatory action of contrathion on ACh release.

  4. 4.

    The complexity of the synaptic action of contrathion raises the possibility that its therapeutic effects in AChE poisonings are not limited to AChE reactivation.

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References

  • Adams, D. J., Gage, P. W., and Hamill, O. P. (1982). Inhibitory postsynaptic currents atAplysia cholinergic synapses: Effects of permeant anions and depressant drugs.Proc. R. Soc. Lond. B. 214335–350.

    Google Scholar 

  • Adams, P. R., and Sakmann, B. (1978). Decamethonium both opens and blocks endplate channels.Proc. Natl, Acad. Sci. USA 752994–2998.

    Google Scholar 

  • Alkondon, M., Rao, K. S., and Albuquerque, E. X. (1988). Acetylcholinesterase reactivators modify the functional properties of the nicotinic acetylcholine receptor ion channel.J. Pharmacol. Exp. Ther. 245543–556.

    Google Scholar 

  • Amitai, G., Kloog, Y., Balderman, D., and Sokolovsky, M. (1980). The interaction of bis-pyridinium oximes with mouse brain muscarinic receptor.Biochem. Pharmacol. 29483–488.

    Google Scholar 

  • Anderson, D.C., King, S. C., and Parsons, S. M. (1983). Pharmacological characterization of the acetylcholine transport system in purifiedTorpedo electric organ synaptic vesicles.Mol. Pharmacol. 2448–54.

    Google Scholar 

  • Baux, G., and Tauc, L. (1983). Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter.Proc. Natl. Acad. Sci. USA 805126–5128.

    Google Scholar 

  • Baux, G., and Tauc, L. (1987). Presynaptic actions of curare and atropine on quantal acetylcholine release at a central synapse ofAplysia.J. Physiol. 388665–680.

    Google Scholar 

  • Baux, G., Poulain, B., and Tauc, L. (1986). Quantal analysis of action of hemicholinium-3 studied at a central cholinergic synapse ofAplysia.J. Physiol. 380209–226.

    Google Scholar 

  • Baux, G., Poulain, B., Fossier, P., and Tauc, L. (1987). Mise en évidence d'autorécepteurs muscariniques et nicotiniques régulant la libération d'acétylcholine au niveau d'une synapse centrale identifiée d'aplysie.C.R. Seances Acad. Sci. Ser. III 304365–368.

    Google Scholar 

  • Brezenhoff, H. E., McGee, J., and Hymowitz, N. (1985). Effect of soman on shedule-controlled behavior and brain acetylcholinesterase in rats.Life Sci. 372421–2430.

    Google Scholar 

  • Broomfield, C., Dembure, I. J., and Cuculis, J. (1987). Binding of soman antidotes to acetylcholine receptors.Biochem. Pharmacol. 361017–1022.

    Google Scholar 

  • Caratsch, C. G., and Waser, P. G. (1984). Effects of obidoxime chloride on native and sarin-poisoned frog neuromuscular junctions.Pflugers Arch. Eur. J. Physiol. 40184–90.

    Google Scholar 

  • Changeux, J. P., Devillers-Thiery, A., and Chermouilli, P. (1984). Acetylcholine receptor: An allosteric protein.Science 3351335–1345.

    Google Scholar 

  • Child, A. F., Davies, D. R., Green, H. L., and Rutland, J. P. (1955). The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organophosphorous compounds.Br. J. Pharm. Chemother. 10462–465.

    Google Scholar 

  • Coyne, M. D., Dagan, D., and Levitan, I. B. (1987). Calcium and barium permeable channels fromAplysia nervous system reconstituted in lipid bilayers.J. Membr. Biol. 97205–213.

    Google Scholar 

  • du Toit, P. W., Muller, P. O., Van Tonder, W. M., and Ungerer, M. J. (1981). Experience with the intensive care management of organophosphate poisoning.S. Afr. Med. J. 60227–229.

    Google Scholar 

  • Edwards, C., and Ikeda, K. (1962). Effects of 2-PAM and succinylcholine on neuromuscular transmission in the frog.J. Pharmacol. Exp. Ther. 138322–328.

    Google Scholar 

  • Eisenstadt, M. L., Treistman, S. N., and Schwartz, J. H. (1975). Metabolism of acetylcholine in the nervous system ofAplysia californica. II. Regional localization and characterization of choline uptake,J. Gen. Physiol. 65275–291.

    Google Scholar 

  • Ellin, R. I. (1982). Anomalies in theories and therapy of intoxication by potent organophosphorous anticholinesterase compounds.Gen. Pharmacol. 13457–466.

    Google Scholar 

  • Ellin, R. I., Groff, W. A., and Sidell, F. R. (1974). Passage of pyridinium oximes into human red cells.Biochem. Pharmacol. 232663–2670.

    Google Scholar 

  • Fernando, J. C., Hoskins, B. H., and Ho, I. K. (1984). A striatal serotonergic involvement in the behavioral effects of acetylcholinesterase organophosphates.Eur. J. Pharmacol. 98129–132.

    Google Scholar 

  • Forman, S. A., and Miller, K. W. (1988). High acetylcholine concentrations cause rapid inactivation before fast desensitization in nicotinic acetylcholine receptors fromTorpedo.Biophys. J. 54149–158.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1983a). Possible role of acetylcholinesterase in regulation of postsynaptic receptor efficacy at a central inhibitory synapse ofAplysia.Nature 301710–712.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1983b). Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse.Pflugers Arch. Eur. J. Physiol. 39615–22.

    Google Scholar 

  • Fossier, P., Tauc, L., and Baux, G. (1983c). Side effects of phosphorylated acetylcholinesterase reactivators on neuronal membrane and synaptic transmission.Pflugers Arch. Eur. J. Physiol. 3968–14.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1985). Acetylcholinesterase and synaptic efficacy. In Alkon, D. L., and Wood, C. D. (Eds.),Neural Mechanisms of Conditioning, Plenum Press, New York, Vol. 24, pp. 341–354.

    Google Scholar 

  • Fossier, P., Poulain, B., Baux, G., and Tauc, L. (1988). Both presynaptic nicotinic-like and muscarinic-like autoreceptors regulate acetylcholine release at an identified neuro-neuronal synapse ofAplysia.Pflugers Arch. Eur. J. Physiol. 411345–352.

    Google Scholar 

  • Gardner, D., Ruff, R. L., and White, R. L. (1984). Choline acts as agonist and blocker forAplysia cholinergic synapses.J. Neurophysiol. 511–15.

    Google Scholar 

  • Goyer, R. G. (1970). The effects of P-2-AM on the release of acetylcholine from the isolated diaphragm of the rat.J. Pharm. Pharmacol. 2242–45.

    Google Scholar 

  • Green, M. D., Reid, F., and Kaminskis, A. (1985). Correlation of 2-PAM plasma levels after organophosphate intoxication.Res. Commun. Chem. Pathol. Pharmacol. 49255–266.

    Google Scholar 

  • Gupta, R. C., Patterson, G. T., and Dettbarn, W. D. (1986). Mechanisms of toxicity and tolerance to diisopropylphosphofluoridate at the neuromuscular junction.Toxicol. Appl. Pharmacol. 84541–550.

    Google Scholar 

  • Harris, L. W., Fleisher, J. H., and Yamamura, H. I. (1971). Effects of 2-PAMC1 and toxogonin on retinal and brain acetylcholinesterase inhibited by sarin.Eur. J. Pharmacol. 1438–46.

    Google Scholar 

  • Hobbiger, F. (1976). Pharmacology of anticholinesterase drugs.Handbk. Exp. Pharmacol. 42487–582.

    Google Scholar 

  • Holland, P., Parkes, D., and Shakespeare, J. (1972). Concentrations of the oxime 2-hydroxy-iminomethyl pyridinium methyl methanesulfonate, P2S after intramuscular injection in humans.Br. J. Pharmacol. 44:368 P.

    Google Scholar 

  • Hopff, W. H., and Waser, P. G. (1970). Warum können Reaktivatoren schädlich sein? Abgehandelt am Beispiel der Reaktivierung der blockierten Acetylcholinesterase.Pharm. Acta Helv. 45414–423.

    Google Scholar 

  • Hopff, W. H., Riggio, G., and Waser, P. G. (1984). Sarin poisoning in guinea pigs compared to reactivation of acetylcholinesterasein vitro as a basis for therapy.Acta Pharmacol. Toxicol. 551–5.

    Google Scholar 

  • Ikemoto, Y., and Akaike, N. (1988). Kinetic analysis of acetylcholine-induced chloride current in isolatedAplysia neurones.Pflugers Arch. Eur. J. Physiol. 412240–247.

    Google Scholar 

  • Jager, B., Staff, V., Green, G. N., and Jager, L. (1958). Studies on distribution and disappearance of pyridine-2-aldoxime methiodide, PAM, and of diacetyl monoxime, DAM, in man and experimental animals.Johns Hopkins Hosp. Bull. 102225–234.

    Google Scholar 

  • Katz, B., and Miledi, R. (1972). The statistical nature of the acetylcholine potential and its molecular components.J. Physiol. 224665–700.

    Google Scholar 

  • Katz, B., and Thesleff, S. (1957). A study of the “desensitization” produced by acetylcholine at the motor end-plate.J. Physiol. 13863–80.

    Google Scholar 

  • Kehoe, J. (1972). Three acetylcholine receptors inAplysia neurones.J. Physiol. 225115–146.

    Google Scholar 

  • Kirsch, D. M., and Weger, N. (1981). Effects of the bisquaternary compounds HGG 12, HGG 42 and obidoxime on synaptic transmission and NAD(P)H fluorescence in the superior cervical ganglion of the ratin vivo.Arch. Toxicol. 47217–232.

    Google Scholar 

  • Kloog, Y., and Sokolovsky, M. (1985a). Bisquaternary pyridinium oximes as allosteric inhibitors of rat brain muscarinic receptors: Selective effects on antagonist binding and loss of receptor binding sites.Mol. Pharmacol. 27418–428.

    Google Scholar 

  • Kloog, Y., and Sokolovsky, M. (1985b). Allosteric interaction between muscarinic agonist binding sites and effector sites demonstrated by the use of bisquaternary pyridinium oximes.Life Sci. 362127–2136.

    Google Scholar 

  • Kloog, Y., Galron, R., Balderman, D., and Sokolovsky, M. (1985). Reversible and irreversible inhibition of rat brain muscarinic receptors is related to different substitutions on bisquaternary pyridinium oximes.Arch. Toxicol. 5837–39.

    Google Scholar 

  • Kloog, Y., Galron, R., and Sokolovsky, M. (1986). Bisquaternary pyridinium oximes as presynaptic agonists and postsynaptic antagonists of muscarinic receptors.J. Neurochem. 46767–722.

    Google Scholar 

  • Kuhnen-Clausen, D., Hagedorn, I., Gross, G., Bayer, H., and Hucho, F. (1983). Interactions of bisquaternary pyridine salts, H-oximes, with cholinergic receptors.Arch. Toxicol. 54171–179.

    Google Scholar 

  • Laskowski, M. B., and Dettbarn, W. D. (1975). Presynaptic effects of cholinesterase inhibition.J. Pharmacol. Exp. Ther. 194351–361.

    Google Scholar 

  • Laskowski, M. B., and Dettbarn, W. D. (1979). An electrophysiological analysis of the effects of paraoxon at the neuromuscular junction.J. Pharmacol. Exp. Ther. 210269–274.

    Google Scholar 

  • Laskowski, M. B., Olson, W. H., and Dettbarn, W. D. (1975). Ultrastuctural changes at the motor end-plate produced by an irreversible cholinesterase inhibitor.Exp. Neurol. 47290–306.

    Google Scholar 

  • Laskowski, M. B., Olson, W. H., and Dettbarn, W. D. (1977). Initial ultrastructural abnormalities at the motor end-plate produced by a cholinesterase inhibitor.Exp. Neurol. 5713–33.

    Google Scholar 

  • Lundy, P. M., and Trembley, K. P. (1979). Ganglion blocking properties of some bispyridinium soman antagonists.Eur. J. Pharmacol. 6047–53.

    Google Scholar 

  • Marshall, I. G., and Parsons, S. M. (1987). The vesicular acetylcholine transport system.Trends Neurosci. 10174–177.

    Google Scholar 

  • Miller, R. J. (1985). How many types of calcium channels exist in neurones?Trends Neurosci. 845–47.

    Google Scholar 

  • Muller, D. (1986). Potentiation by 4-aminopyridine of quantal acetylcholine release at theTorpedo nerve-electroplaque junction.J. Physiol. 379479–493.

    Google Scholar 

  • Poulain, B., Baux, G., and Tauc, L. (1986). Presynaptic transmitter content controls the number of quanta released at a neuro-neuronal cholinergic synapse.Proc. Natl. Acad. Sci. USA 83170–173.

    Google Scholar 

  • Poulain, B., Fossier, P., Baux, G., and Tauc, L. (1987). Hemicholinium-3 facilitates the release of acetylcholine by acting on presynaptic nicotinic receptors at a central synapse inAplysia.Brain Res. 43563–70.

    Google Scholar 

  • Prinz, H. J. (1969). Eine schwere percutane Vergiftung mit Parathion.Arch. Toxicol. 25318–328.

    Google Scholar 

  • Simonneau, M., and Tauc, L. (1987). Properties of miniature postsynaptic currents during depolarization-induced release at a cholinergic neuronal synapse.Cell. Mol. Neurobiol. 7175–189.

    Google Scholar 

  • Simonneau, M., Tauc, L., and Baux, G. (1980). Quantal release of acetylcholine examined by current fluctuation analysis at an identfied neuro-neuronal synapse ofAplysia.Proc. Natl. Acad. Sci. USA 771661–1665.

    Google Scholar 

  • Slater, N. T., Hall, A. F., and Carpenter, D. O. (1984). Kinetic properties of cholinergic desensitization inAplysia neurons.Proc. R. Soc. Lond. B 22363–78.

    Google Scholar 

  • Sundwall, A. (1961). Minimum concentrations of N-methylpyridinium-2-aldoxime methanesulfonate (P2S) which reverse neuromuscular block.Biochem. Pharmacol. 8413–417.

    Google Scholar 

  • Takeyasu, K., Shiono, S., Udgaonkar, J. B., Fujita, N., and Hess, G. P. (1986). Acetylcholine receptor: Characterization of the voltage dependent regulatory, inhibitory site for acetylcholine in membrane vesicles fromTorpedo californica electroplax.Biochemistry 251770–1776.

    Google Scholar 

  • Tauc, L. (1982). Nonvesicular release of neurotransmitter.Physiol. Rev. 62857–893.

    Google Scholar 

  • Tauc, L., and Baux, G. (1985). Mechanisms of acetylcholine release at neuroneuronal synapses. In Rothman, S. S., and Ho, J. L. (Eds.),Non Vesicular Release, John Wiley and Sons, New York, pp. 253–259.

    Google Scholar 

  • Tauc, L, and Bruner, J. (1963). “Desensitization” of cholinergic receptors by acetylcholine in molluscan central neurons.Nature 19833–34.

    Google Scholar 

  • Tauc, L., and Gerschenfeld, H. M. (1961). Cholinergic transmission mechanisms for both excitation and inhibition in molluscan nervous system.Nature 192366–367.

    Google Scholar 

  • Tiedt, T. N., Albuquerque, E. X., Hudson, C. S., and Rash, J. E. (1978). Neostigmine-induced alterations at the mammalian neuromuscular junction. I. Muscle contraction and electrophysiology.J. Pharmacol. Exp. Ther. 205326–339.

    Google Scholar 

  • Trautmann, A. (1982). Curare can open and block ionic channels associated with cholinergic receptors.Nature 298272–275.

    Google Scholar 

  • Tremblay, J. P., Grenon, G., and Plourde, G. (1980). The effects of hemicholinium-3 on synaptic depression, facilitation, and post-tetanic potentiation at an identified synapse ofAplysia californica, Can.J. Physiol. Pharmacol. 58373–383.

    Google Scholar 

  • White, R. L., and Gardner, D. (1983). Physostigmine prolongs the elementary events underlying decay of inhibitory postsynaptic currents inAplysia.J. Neurosci. 32607–2613.

    Google Scholar 

  • Wilson, I. B., and Ginsburg, S. (1955). A powerful reactivator of alkyl phosphate inhibited acetylcholinesterase.Biochim. Biophys. Acta 18168–170.

    Google Scholar 

  • Wirth, W. (1968). Schädigungsmöglichkeiten durch Antidote.Arch. Toxicol. 2471–82.

    Google Scholar 

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Fossier, P., Baux, G., Poulain, B. et al. Receptor-mediated presynaptic facilitation of quantal release of acetylcholine induced by pralidoxime inAplysia . Cell Mol Neurobiol 10, 383–404 (1990). https://doi.org/10.1007/BF00711182

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