Peripheral catecholamine release by α-latrotoxin in the rat

Summary

Intraarterial injection of α-latrotoxin (αLTx), the major toxin of the black widow spider (Latrodectus mactans tredecimguttatus) venom, into carotid catheterized rats, induced prompt and marked rises in plasma adrenaline and noradrenaline concentrations, indicating that the toxin stimulates catecholamine release from both the adrenal medulla and sympathetic nerve terminals. Pretreatment with the ganglionic blocker chlorisondamine greatly reduced the plasma adrenaline response to αLTx but had almost no effect on the noradrenaline response, indicating that αLTx-stimulation of sympathetic nerve terminals is direct, whereas catecholamine release from the adrenal medulla is probably mediated by preganglionic release of acetylcholine. In vitro, αLTx induced a dose-dependent release of ³H-noradrenaline from rat irides preincubated with this radioactive amine and this effect was not changed by chlorisondamine plus atropine. By contrast, the toxin had no effect on ³H-noradrenaline release from suspensions of cultured rat chromaffin cells. Specific, high affinity binding of ¹²⁵I-αLTx in iris and adrenal medulla homogenates was found to be exceedingly low, suggesting that it might be restricted to nerve terminals. No ¹²⁵I-αLTx binding was seen nor could any effect of the toxin on ¹⁴C-5-hydroxytryptamine release be found in rat blood platelet preparations. αLTx binding and its amine releasing effect seem, therefore, to be specific for neurons and absent from other cells, even those, like adrenomedullary cells and blood platelets, which share with neurons their origin and/or other important characteristics.