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Depolarization increases inositolphosphate production in a particulate preparation from rat brain

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Summary

We have studied the accumulation of inositol phosphates (InsP) due to depolarization. A particulate preparation of rat brain was introduced to rule out transmitter activated mechanisms and to allow free access for drugs of high molecular weights.

Potassium depolarization doubled InsP within a few minutes. InsP accumulation depended on time and K+ concentration, and was affected neither by tetrodotoxin nor by atropine. Radioactive metabolites co-eluted with inositol mono-phosphate and inositol bis-phosphate, whereas only minor amounts appeared with inositol tris-phosphate. The content in phosphatidylinositols was decreased. No evidence was found for the involvement of a neurotransmitter.

Sea anemone toxin II (around 1 μmol/l), which keeps the Na+-channels open, promoted the InsP accumulation in an atropine-resistant manner. Tetrodotoxin prevented it when given before, and inhibited it when given after initiation by sea anemone toxin II. Moreover the K+ channel blockers 4-aminopyridine, dendrotoxin and tetraethylammonium all caused InsP accumulation.

Palytoxin was by far the most potent promoter of InsP accumulation with a detection limit below 10 pmol/l, and displayed a unique bell-shaped concentration-effect correlation. Ouabain (3 μmol/l) and above) also elicited the InsP accumulation.

The response to carbachol was not only inhibited completely by atropine, but also partially (more than 50%) by tetrodotoxin, which indicates the involvement of voltage-dependent sodium channels in the receptor-triggered InsP accumulation.

Thus independent of the causative agent, depolarization promotes an InsP accumulation. We conclude that degradation of phosphatidylinositols is mediated not only by receptor occupation but also by a positive shift in membrane voltage.

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Authors and Affiliations

  1. Rudolf-Buchheim-Institut für Pharmakologie, Justus-Leibig-Universität, Frankfurter Strasse 107, D-6300, Giessen, Federal Republic of Germany

    E. Habermann & M. Laux

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  1. E. Habermann
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  2. M. Laux
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Abbreviations (according to Berridge and Irvine 1984, and Cockfort and Gomperts 1985). InsP, inositol phosphates; InsP1, inositol mono-phosphate; InsP2, inositol bis-phosphate; InsP3, inositol tris-phosphate. Since the techniques used did not distinguish the various possible isomers, any references to the position of the phosphates were omitted. PtdIns, phosphatidylinositols; PtdInsP1, phosphatidylinositolphosphate; PtdInsP2, phosphatidylinositol bis-phosphate. ATX II, sea anemone toxin II. TTX, tetrodotoxin. GABA, γ-amino butyric acid

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Habermann, E., Laux, M. Depolarization increases inositolphosphate production in a particulate preparation from rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 334, 1–9 (1986). https://doi.org/10.1007/BF00498733

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  • DOI: https://doi.org/10.1007/BF00498733

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