Summary
cAMP and cGMP were measured in mouse cerebellar slices, neural cell lines and primary nerve cell cultures from rats after treatment with different neurotoxins and high potassium.
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1.
Sea anemone toxin II (ATX II), which is known to keep the activated sodium channels open, raised the cGMP content of mouse cerebellar slices up to 35-fold and doubled their cAMP content. Mast-cell-degranulating peptide (MCD-peptide) from been venom increased cGMP levels up to 15-fold. The effects of both toxins on the cyclic nucleotide content were mimicked by depolarizing agents, like high potassium and veratridine.
Primary nerve cell cultures (4 weeks old) responded to ATX II and high potassium with an increase of both cGMP and cAMP, however to a smaller extent as compared with slices. Excitable structures appear to be relevant, because younger cultures (2 weeks and less) and several neural cell lines did not respond to ATX II.
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2.
Specific neurotoxins like tetanus toxin, botulinum A toxin and apamin from bee venom had no effect on the cyclic nucleotide content of cerebellar slices and of primary nerve cell cultures. In cerebellar slices the potassium-stimulated increase of cAMP and cGMP was not affected by previous exposure of the slices to tetanus toxin or apamin.
We conclude that opening of sodium channels in excitable membranes generally raises the cyclic nucleotide content whereas the mode of action of specific neurotoxins is not reflected by changes in the overall content of cyclic nucleotides.
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Abbreviations
- cAMP:
-
3′,5′-cyclic adenosine monophosphate
- cGMP:
-
3′,5′-cyclic guanosine monophosphate
- ATXII:
-
sea anemone toxin II
- MCD-peptide:
-
mast cell degranulating peptide
- IBMX:
-
3-isobutyl 1-methyl xanthine
- PDE (EC 3.1.4.17):
-
3′,5′-cyclic nucleotide phosphodiesterase
- Hepes:
-
N-2′-hydroxyethyl-piperazin-2-ethane sulfonic acid
- KRBG:
-
Krebs-Ringer-bicarbonate with glucose
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Ahnert, G., Glossmann, H. & Habermann, E. Effects of ion channel toxins and specific neurotoxins on the cyclic nucleotide content of cerebellar slices, primary brain cultures and neural cell lines. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 151–157 (1979). https://doi.org/10.1007/BF00498457
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DOI: https://doi.org/10.1007/BF00498457