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The effects of protoveratrine and germines on the release of acetylcholine from the auerbach plexus of the guinea-pig ileum

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Summary

The effect of protoveratrine A and germine-3-acetate (GMA) on the release mechanism of acetylcholine from the nerve terminals of the Auerbach plexus in the longitudinal muscle layer of the guinea-pig ileum was studied. Protoveratrine A, GMA and germine potentiated neuroeffector transmission in Auerbach's plexus in the longitudinal muscle preparation provided the neurons were stimulated at low frequencies (< 10 Hz).

Protoveratrine A and GMA enhanced the release of acetylcholine from the nerve terminals during the resting period and at low frequency of stimulation (< 10 Hz). At continous stimulation with high frequency they were ineffective (> 10 Hz).

When trains of 20 stimuli, with a pulse interval of 0.1 s (10 Hz) were repeatedly applied with intervals of 0.1 to 20 s between trains, the effect of GMA to increase ACh release depended on the length of the train interval; the longer the resting period between trains the higher was the output of ACh. This fact indicates that the release of ACh increased primarily during the resting periods following single stimuli or trains.

The effect of GMA on ACh release proved to be highly temperature-dependent: in the presence of GMA Q10 increasing from 3.25 to 4.92.

A high Ca concentration, removal of Mg or lowering of the Na concentration abolished the effect of GMA to enhance ACh release.

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References

  • Baker, P. F., A. L. Hodgkin, andI. I. Shaw: The effects of changes in internal ionic concentrations on the electrical properties of perfused giant axons. J. Physiol. (Lond.)164, 355–374 (1962).

    Google Scholar 

  • Brading, A., E. Bülbring, andT. Tomita: The effect of sodium and calcium on the action potential of the smooth muscle of the guinea pig taenia coli. J. Physiol.200, 637–654 (1969).

    Google Scholar 

  • Brennan, J. L., S. F. Jones, andJ. G. McLeod: Effect of germine acetates on neuromuscular transmission. J. Neurol. Sci.13, 321–331 (1971).

    Google Scholar 

  • Bülbring, E., andH. Kuriyama: Effects of changes in the external sodium and calcium concentrations on spontaneous electrical activity in smooth muscle of guinea pig taenia coli. J. Physiol. (Lond.)166, 29–58 (1963).

    Google Scholar 

  • Detwiler, P. B.: The effects of germine-3-acetate on neuromuscular transmission. J. Pharmacol. Exp. Ther.180, 244–254 (1972).

    Google Scholar 

  • Flacke, W.: Studies on veratrum alkaloids. XXXVI. The action of germine diacetate on mammalian skeletal muscle. J. Pharmacol. Exp. Ther.141, 230–236 (1963).

    Google Scholar 

  • Flacke, W. E., R. P. Blume, W. R. Scott, F. F. Foldes, andK. E. Osserman: Germine monoand diacetate in myasthenia gravis. Ann. N.Y. Acad. Sci.183, 316–333 (1971).

    Google Scholar 

  • Flacke, W., V. S. Caviness, andF. G. Samaha: Treatment of myasthenia gravis with germine diacetate. N. Eng. J. Med.275, 1207–1214 (1966).

    Google Scholar 

  • Flacke, W., R. L. Katz, J. W. Flacke, andM. H. Alper: Germine diacetate as an antagonist of depolarizing and nondepolarizing neuromuscular blocking agents in man. Anesthesiology29, 850–854 (1968).

    Google Scholar 

  • Foldes, F. F., E. B. Brodman, H. N. Kranzler, P. S. Underwood, andB. A. Hemsworth: The effects of germine diacetate on the rat phrenic nerve-diaphragm preparation. Anesthesiology31, 522–531 (1969).

    Google Scholar 

  • Foldes, F. F., K. Fukushima, E. B. Brodman, andP. S. Underwood: The effect of germine-3-monoacetate (GMA) on the rat phrenic nerve diaphragm preparation. Acta Anaesth. Scandinav. 1970, Suppl. XXXVII, pp. 233–237.

  • Fong, T. P.: The production of prolonged after-discharge in nerve by veratrine. Chinese J. Physiol.16, 207 (1941). Cit.Krayer andAcheson (1946).

    Google Scholar 

  • Gabella, G.: Fine structure of the myenteric plexus in the guinea-pig ileum. J. Anat. III, 69–97 (1972).

    Google Scholar 

  • Ginsborg, B. L., andJ. T. Hamilton: The effect of calcium ions on neuromuscular transmission in the frog. Q. J. Exp. Physiol.53, 162–169 (1968).

    Google Scholar 

  • Goldman, W. J., andA. Scriabine: Some effects of germine-3-monoacetate (GMA) on isolated rat and guinea-pig ileum. J. Pharmacol. Exp. Ther.177, 181–187 (1971).

    Google Scholar 

  • Graham, H. R., andH. S. Gasser: Modification of nerve response by veratrine and aconitine. J. Pharmacol. Exp. Ther.43, 163–185 (1931).

    Google Scholar 

  • Hofmann, W. W.: Action of veratrine on human skeletal muscle with special reference to myasthenia gravis. Neurology (Minneap.)8, 917–932 (1958).

    Google Scholar 

  • Hofmann, W. W.: Newer drugs for myasthenis gravis; A microphysiologic study of effects. J. Pharmacol. Exp. Ther.160, 349–359 (1968).

    Google Scholar 

  • Katz, B., andR. Miledi: The release of acetylcholine from nerve endings by grading electric pulses. Proc. Roy. Soc. (Biol.)167, 23–38 (1967).

    Google Scholar 

  • Ková.cs, T., B. Szabó, andE, Varga: Effect of veratrine on the24Na exchange of frog sartorius. Acta Physiol. Hung.43, 167–178 (1973).

    Google Scholar 

  • Knoll, J., andE. S. Vizi: Effect of frequency of stimulation on the inhibition by noradrenaline of the acetylcholine output from parasympathetic nerve terminals. Brit. J. Pharmacol.42, 263–272 (1971).

    Google Scholar 

  • Krayer, O., andG. H. Acheson: The pharmacology of the veratrum alkaloids. Physiol. Rev.26, 283–446 (1946).

    Google Scholar 

  • Kuffler, S. W.: Action of veratrine on nerve muscle preparations. J. Neurophysiol.8, 113–122(1945).

    Google Scholar 

  • Lundberg, A.: On the effect of temperature on the depolarization of frog nerve fibres. Acta Physiol. Scand.22, 348–364 (1951).

    Google Scholar 

  • Narahashi, I., J. W. Moore, andW. R. Scott: Tetrodotoxin blockade of sodium conductance increase in lobster giant axons. J. Gen. Physiol.49, 965–974 (1964).

    Google Scholar 

  • Okamoto, K., andJ. H. Quastel: Tetrodotoxin-sensitive uptake of ions and water by slices of rat brain in vitro. Biochem. J.120, 37–47 (1970).

    Google Scholar 

  • Paton, W. D. M., andE. S. Vizi: The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig longitudinal muscle strip. Br. J. Pharmacol.35, 10–28 (1969).

    Google Scholar 

  • Paton, W. D. M., E. S. Vizi, andM. A. Zar: The mechanism of acetylcholine release from parasympathetic nerves. J. Physiol. (Lond.)215, 819–848 (1971).

    Google Scholar 

  • Shanes, A. M.: Electrochemical aspects of physiological and pharmacological action in excitable cells. Pharmac. Rev.10, 59–273 (1958).

    Google Scholar 

  • Standaert, F. G., andP. B. Detwiler: The neuromuscular pharmacology of germine-3-acetate and germine-3,16-diacetate. J. Pharmacol. Exp. Ther.171, 223–241 (1970).

    Google Scholar 

  • Straub, R.: Die Wirkungen von Veratridin und Ionen auf das Ruhepotential markhaltiger Nervenfasern des Frosches. Helv. Physiol. Acta14, l-28 (1956).

    Google Scholar 

  • Ulbricht, W.: Effect of temperature on the slowly changing permeability of veratrinized nodes of Ranvier. Pflügers Arch.31, 73–95 (1969 a).

    Google Scholar 

  • Ulbricht, W.: The effect of veratridine on excitable membranes of nerve and muscle. Ergebn. Physiol.61, 18–71 (1969 b).

    Google Scholar 

  • Ulbricht, W., andW. Flacke: After-potentials and large depolarizations of single nodes of Ranvier treated with veratridine. J. Gen. Physiol.48, 1035–1046 (1965).

    Google Scholar 

  • Varga, E., L. Kovćs, andJ. Geszthelyi: Depolarizing effect of veratrine on frog skeletal muscle. Acta Physiol. Hung.41, 81–93 (1972 a).

    Google Scholar 

  • Varga, E., T. Kovács, andB. Szabó: The effect of veratrine on ion transport in frog skeletal muscle. Acta Physiol. Hung.41, 265–277 (1972 b).

    Google Scholar 

  • Vizi, E. S., P. Illés, A. Rónai, andJ. Knoll: The effect of lithium on acetylcholine release and synthesis. Neuropharm.11, 521–526 (1972).

    Google Scholar 

  • Vizi, E. S., G. Bertaccini, M. Impicciatore, P. Mantovani, J. Zséli, andJ. Knoll: Structure-activity relationship of some analogues of gastrin and cholecytokinin on intestinal smooth muscle of the guinea-pig. Naunyn-Schmiedeberg's Arch. Pharmac.284, 233–243 (1974).

    Google Scholar 

  • Wright, E., andT. Tomita: Study of the crustacean axon repetitive response. A comparison of the effect of veratrine sulfate solution and potassium-rich solution. J. Cell. Physiol.67, 181–196 (1966).

    Google Scholar 

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Author notes

  1. E. S. Vizi

    Present address: Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary

  2. J. Theunissen

    Present address: Department of Pharmacology, Nijmegen University, The Netherlands

Authors and Affiliations

  1. Laboratory of Neurophysiology, Department of Anaesthesiology, Montefiore Hospital and Medical Center, New York, USA

    E. S. Vizi, F. F. Foldes & J. Theunissen

  2. Department of Anaesthesiology, Albert Einstein College of Medicine, New York, USA

    E. S. Vizi, F. F. Foldes & J. Theunissen

Authors
  1. E. S. Vizi
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  2. F. F. Foldes
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  3. J. Theunissen
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Vizi, E.S., Foldes, F.F. & Theunissen, J. The effects of protoveratrine and germines on the release of acetylcholine from the auerbach plexus of the guinea-pig ileum. J. Neural Transmission 37, 43–60 (1975). https://doi.org/10.1007/BF01249765

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  • DOI: https://doi.org/10.1007/BF01249765

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