Inhibition of catecholamine secretion from adrenal medulla cells by neurotoxins and cholinergic antagonists.
The effects of several neurotoxins and cholinergic antagonists on the nicotine-induced secretion of catecholamines by adrenal medulla cells in culture were investigated. Aconitine, veratridine, and batrachotoxin, in the presence of 1 micrometer-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 also increases the flux of Na+ through tetrodotoxin-sensitive channels, was not an effective inhibitor of nicotine-stimulated secretion. Histrionicotoxin, atropine, hexamethonium, and decamethonium--as well as the Na+-channel activators--noncompetitively inhibit nicotine-stimulated secretion. The effects of these agents on nicotine-stimulated secretion appears similar to their effects on the inhibition of depolarization at the neuromuscular junction. Reversibility studies suggest that the stimulatory and inhibitor sites of the neurotoxins are different, while studies in Na+-free media suggest that tetrodotoxin-insensitive sodium channels are not involved in the inhibitory effect of the neurotoxins. A possible site of action for the inhibitory effects of the neurotoxins. A possible site of action for the inhibitory effects of the neurotoxins is the nicotinic-receptor-associated ion channel.
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001496:Batrachotoxins / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D001496:Batrachotoxins; D002395:Catecholamines; D009498:Neurotoxins; D013779:Tetrodotoxin; D009538:Nicotine; D014701:Veratridine; D001285:Atropine; D000109:Acetylcholine