Inhibition of Catecholamine Secretion from Adrenal Medulla Cells by Neurotoxins and Cholinergic Antagonists

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Abstract
The effects of several neurotoxins and cholinergic antagonists on the nicotine-induced secretion of catecholamines by bovine adrenal medulla cells in culture were investigated. Aconitine, veratridine and batrachotoxin, in the presence of 1 .mu.M-tetrodotoxin inhibited the nicotine-stimulated secretion of catecholamines in a dose-dependent manner in Locke''s solution. In Na+-free sucrose medium, tetrodotoxin was not required to inhibit the stimulatory effects of aconitine, veratridine and batrachotoxin and these agents by themselves inhibited the nicotine-stimulated secretion of catecholamines. Scorpion venom, which increases the flux of Na+ through tetrodotoxin-sensitive channels, was not an effective inhibitor of nicotine-stimulated secretion. Histrionicotoxin, atropine, hexamethonium and decamethonium and the Na+-channel activators noncompetitively inhibit nicotine-stimulated secretion. The effects of these agents on nicotine-stimulated secretion appear similar to their effects on the inhibition of depolarization at the neuromuscular junction. Reversibility studies suggest that the stimulatory and inhibitory sites of the neurotoxins are different; studies in Na+-free media suggest that tetrodotoxin-insensitive Na channels are not involved in the inhibitory effect of the neurotoxins. A possible site of action for the inhibitory effects of the neurotoxins is the nicotinic-receptor-associated ion channel.