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Investigations on the mechanism of cyclic guanosine monophosphate increase due to depolarizing agents as studied with sea anemone toxin II in mouse cerebellar slices

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Summary

Sea anemone toxin II (ATX II) and MCD-peptide, like other depolarizing agents, raise the content of cGMP and to a lesser extent of cAMP in mouse cerebellar slices. Na+ influx and Ca2+ movement are involved in their mode of action, as indicated by the following observations:

  1. 1.

    The rise of cGMP due to ATX II, MCD-peptide and high potassium was diminished when Na+ had been replaced by Li+.

  2. 2.

    The effects of both toxins and veratridine, but not of high potassium stimulation were prevented by tetrodotoxin (TTX).

  3. 3.

    The cGMP accumulation due to both toxins was abolished in the absence of extracellular Ca2+.

  4. 4.

    The so-called Ca2+-antagonist (−)-D-600 blocked the increase of cGMP due to ATX II, MCD-peptide, veratridine and high potassium.

  5. 5.

    ATX II stimulated the 45Ca2+ uptake in mouse cerebellar slices which was prevented by TTX and (−)-D-600.

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Abbreviations

cAMP:

3′, 5′-cyclic-adenosine monophosphate

cGMP:

3′, 5′-cyclic-guanosine monophosphate

ATX II:

sea anemone toxin II

TTX:

tetrodotoxin

MCD-peptide:

mast cell degranulating peptide

ADA:

adenosine desaminase

D-600:

3-methoxy verapamil

IBMX:

isobutyl methyl xanthine

References

  • Abita, J. P., Chicheportiche, R., Schweitz, H., Lazdunski, M.: Effects of neurotoxins (veratridine, sea anemone toxin, tetrodotoxin) on transmitter accumulation and release by nerve terminals in vitro. Biochemistry 16, 1838–1844 (1977)

    Google Scholar 

  • Ahnert, G., Glossmann, H., Habermann, E.: Effects of ion channel toxins and specific neurotoxins on the cyclic nucleotide content of some neural tissues. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 151–157 (1979)

    Google Scholar 

  • Bayer, R., Kalusche, D., Kaufmann, R., Manhold, R.: Inotropic and electrophysiological actions of verapamil and D-600 in mammalian myocardium. III. Effects of the optical isomers on transmembrane action potentials. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 81–97 (1975)

    Google Scholar 

  • Benjamin, A. M., Quastel, J. H.: Effects of acetylcholine and tetrodotoxin on transport processes of high K+ and protoveratrine-stimulated rat brain cortex slices. Proc. Can. Fed. Biol. Soc. 20, 9 (1977)

    Google Scholar 

  • Blaustein, M. P.: Effects of potassium, veratridine and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro J. Physiol. (Lond.) 247, 617–655 (1975)

    Google Scholar 

  • Daly, J. W.: The formation, degradation, and function of cyclic nucleotides in the nervous system. Int. Rev. Neurobiol. 20, 105–168 (1977)

    Google Scholar 

  • De Barry, J., Fosset, M., Lazdunski, M.: Molecular mechanism of the cardiotoxic action of a polypeptide neurotoxin from sea anemone on cultured embryonic cardiac cells. Biochemistry 16, 3850–3855 (1977)

    Google Scholar 

  • Evans, M. H.: Tetrodotoxin, saxitoxin, and related, substances: their application in neurobiology. Int. Rev. Neurobiol. 15, 83–166 (1972)

    Google Scholar 

  • Ferrendelli, J. A.: Cellular depolarization and cyclic nucleotide content in central nervous system. Adv. Biochem. Psychopharmacol. 15, 303–313 (1976)

    Google Scholar 

  • Ferrendelli, J. A., Kinscherf, D. A., Chang, M. M.: Regulation of levels of guanosine cyclic 3′,5′-monophosphate in the central nervous system: Effects of depolarizing agents. Mol. Pharmacol. 9, 445–454 (1973)

    Google Scholar 

  • Ferrendelli, J. A., Chang, M. M., Kinscherf, D. A.: Elevation of cyclic GMP levels in central nervous system by excitatory and inhibitory amino acids. J. Neurochem. 22, 535–540 (1974)

    Google Scholar 

  • Ferrendelli, J. A., Kinscherf D. A., Chang, M. M.: Comparison of the effects of biogenic amines on cGMP and cAMP levels in mouse cerebellum in vitro. Brain Res., 84, 63–73 (1975)

    Google Scholar 

  • Ferrendelli, J. A., Rubin, H., Kinscherf, D. A.: Influence of divalent cations on regulation of cyclic GMP and cyclic AMP levels in brain tissue. J. Neurochem. 26, 741–748 (1976)

    Google Scholar 

  • Fosset, M., De Barry, J., Lenoir, M.-C., Lazdunski, M.: Analysis of molecular aspects of Na+ and Ca2+ uptakes by embryonic cardiac cells in culture. J. Biol. Chem. 252, 6112–6117 (1977)

    Google Scholar 

  • Goldberg, N. D., Haddox, M. K.: Cyclic GMP metabolism and involvement in biological regulation. Ann. Rev. Biochem. 46, 823–896 (1977)

    Google Scholar 

  • Huang, M., Shimizu, H., Daly, J.: Accumulation of cyclic adenosine monophosphate in incubated slices of brain tissue. 2. Effects of depolarizing agents, membrane stabilizers, phosphodiesterase inhibitors and adenosine analogs. Med. Chem. 15, 462–466 (1972)

    Google Scholar 

  • Huang, M., Gruenstein, E., Daly, J. W.: Depolarization — evoked accumulation of cyclic AMP in brain slices: inhibition by exogenous adenosine deaminase. Biochim. Biophys. Acta 329, 147–151 (1973)

    Google Scholar 

  • Kalix, P., Roch, P.: Effect of depolarizing agents on the adenosine-3′,5′-monophosphate content of the bovine superior cervical ganglion. Naunyn-Schmiedeberg's Arch. Pharmacol. 291, 131–137 (1975)

    Google Scholar 

  • Kebabian, J. W.: Biochemical regulation and physiological significance of cyclic nucleotides in the nervous system. Adv. Cycl. Nucleot. Res. 8, 421–508 (1977)

    Google Scholar 

  • Kinscherf, D. A., Chang, M. M., Rubin, E. H., Schneider, D. R., Ferrendelli, J. A.: Comparison of the effects of depolarizing agents and neurotransmitters on regional CNS cyclic GMP levels in various animals. J Neurochem. 26, 527–530 (1976)

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin-phenol reagent. J. Biol. Chem. 193, 265–275 (1951)

    Google Scholar 

  • Narahashi, T.: Chemicals as tools in the study of excitable membranes. Physiol. Rev. 54, 813–889 (1974)

    Google Scholar 

  • Nathanson, J. A.: Cyclic nucleotides and nervous system function. Physiol. Rev. 57, 157–256 (1977)

    Google Scholar 

  • Ohga, J., Daly, J. W.: Calcium ion-elicited accumulations of cyclic GMP in guinea pig cerebellar slices. Biochim. Biophys. Acta 498, 61–75 (1977)

    Google Scholar 

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

    Google Scholar 

  • Rathmayer, W., Beress, L.: Sea anemone toxin: Investigations on their mode of action. Proceedings of the 5th Int. Symp. on Animal, Plant and Microbial Toxins, pp. 549–556. New York: Pergamon Press 1978

    Google Scholar 

  • Romey, G., Abita, J. P., Schweitz, H., Wunderer, G., Lazdunski, M.: Sea anemone toxin: A tool to study molecular mechanisms of nerve conduction and excitation-secretion coupling. Proc. Natl. Acad. Sci. U.S.A. 73, 4055–4059 (1976)

    Google Scholar 

  • Sattin, A., Rall, T. W.: The effect of adenosine and adenine nucleotides on the cyclic adenosine 3′,5′-phosphate content of guinea pig cerebral cortex slices. Mol. Pharmacol. 6, 13–23 (1970)

    Google Scholar 

  • Schwabe, U., Ohga, Y., Daly, J. W.: The role of calcium in the regulation of cyclic nucleotide levels in brain slices of rat and guinea pig. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 141–151 (1978)

    Google Scholar 

  • Shimizu, H., Daly, J. W.: Effect of depolarizing agents on accumulation of cyclic adenosine 3′,5′-monophosphate in cerebral cortical slices. Eur. J. Pharmacol. 17, 240–252 (1972)

    Google Scholar 

  • Shimizu, H., Yamamura, J.: Effects of diamino-propionate, deoxy adenosine, and theophylline on stimulated formation of cyclic AMP and GMP by depolarizing agents in slices of guinea-pig cerebral cortex. J. Neurochem. 28, 383–388 (1977)

    Google Scholar 

  • Shimizu, H., Creveling, C. R., Daly, J. W.: Effect of membrane depolarization and biogenic amines on the formation of cyclic AMP in incubated brain slices. Adv. Biochem. Psychopharmacol. 3, 135–154 (1970)

    Google Scholar 

  • Shimizu, H. Ichishita, H., Odagiri, H.: Stimulated formation of cyclic adenosine 3′,5′-monophosphate by aspartate and glutamate in cerebral cortical slices of guinea pig. J. Biol. Chem. 249, 5955–5962 (1974)

    Google Scholar 

  • Troyer, E. W., Hall, J. A., Ferrendelli, J. A.: Guanylate cyclase in CNS: enzymatic characteristics of soluble and particulate enzymes from mouse cerebellum and retina. J. Neurochem. 31, 825–833 (1978)

    Google Scholar 

  • Ulbricht, W.: The effect of veratridine on excitable membranes of nerve and muscle. Ergeb. Physiol. Biol. Chem. Exp. Pharmakol. 61, 18–71 (1969)

    Google Scholar 

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Authors and Affiliations

  1. Pharmakologisches Institut der Justus Liebig-Universität Giessen, Frankfurterstrasse 107, D-6300, Lahn-Giessen 1, Federal Republic of Germany

    Gudrun Ahnert, H. Glossmann & E. Habermann

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  1. Gudrun Ahnert
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  2. H. Glossmann
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  3. E. Habermann
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Ahnert, G., Glossmann, H. & Habermann, E. Investigations on the mechanism of cyclic guanosine monophosphate increase due to depolarizing agents as studied with sea anemone toxin II in mouse cerebellar slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 159–166 (1979). https://doi.org/10.1007/BF00498458

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  • DOI: https://doi.org/10.1007/BF00498458

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