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Mechanism of the enhancement in transmitter release from central and peripheral noradrenergic nerve terminals induced by the purified scorpion venom, tityustoxin

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Summary

In the isolated nerve-muscle preparation of the cat nictitating membrane exposure to 0.04 μM of the scorpion venom tityustoxin (TsTX) increased significantly the overflow of 3H-noradrenaline and the responses elicited by postganglionic nerve stimulation (1200 pulses, 0.5 ms duration, supramaximal voltage). Concentration effect curves to exogenous (-)-noradrenaline were not affected in the presence of this concentration of TsTX.

The enhanced release of 3H-noradrenaline obtained during nerve stimulation as well as the increase of the postsynaptic responses observed during exposure to TsTX were more pronounced at 4 Hz than at 20 Hz. The increase in the overflow of noradrenaline observed with the toxin was selective for nerve stimulation since the release evoked by tyramine was not affected by TsTX.

TsTX did not increase further the enhancement of 3H-noradrenaline release obtained in the presence of 18 mM tetraethylammonium (TEA). On the other hand, both TsTX and TEA were able to increase further the overflow of 3H-noradrenaline after block of the presynaptic alpha-adrenoceptors with phenoxybenzamine 0.29 or 2.9 μM.

In slices of rat cerebral cortex, TsTX 0.04 μM increased 3H-noradrenaline release induced by 10 mM and by 20 mM KCl. The increased release evoked by the toxin was more pronounced for the lower concentration of K+.

An increased release of 3H-noradrenaline in the presence of the toxin was also observed in rat hypothalamic slices stimulated with 20 mM K+. The K+ stimulated induced release of 3H-noradrenaline was also increased by 1.8 mM TEA. As shown for the peripheral nervous, system the simultaneous addition of TEA and TsTX did not result in additive effects when compared with the effects of the two agents added separately. Tityustoxin did not modify the metabolic pattern of the neurotransmitter released by K+ from rat hypothalamic slices.

It is concluded that TsTX increases the stimulation-induced release of 3H-noradrenaline from both peripheral and central noradrenergic nerve terminals. Tityustoxin appears to act on the nerve terminal by a mechanism similar to that of TEA, an agent known to enhance the amount of noradrenaline released by nerve stimulation by increasing the duration of the action potentials.

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Author notes

  1. S. Z. Langer

    Present address: Department of Biology, Synthelabo-L.E.R.S., 58, rue de la Glacière, F-75013, Paris, France

Authors and Affiliations

  1. Instituto de Investigaciones Farmacologicas, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Junin 956, 5o Piso, 1113, Buenos Aires, Argentina

    Edda Adler-Graschinsky (Member of the Research Career of the Consejo Nacional de Investigaciones Cientificas y Tecnicas) & S. Z. Langer

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  1. Edda Adler-Graschinsky
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Adler-Graschinsky, E., Langer, S.Z. Mechanism of the enhancement in transmitter release from central and peripheral noradrenergic nerve terminals induced by the purified scorpion venom, tityustoxin. Naunyn-Schmiedeberg's Arch. Pharmacol. 303, 243–249 (1978). https://doi.org/10.1007/BF00498050

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