Anatoxin-a is a potent agonist of the nicotinic acetylcholine receptor of bovine adrenal chromaffin cells

• Published in: European journal of pharmacology 1995-05, Vol.289 (3), p.447-453
• Main Authors: Molloy, Leah, Wonnacott, Susan, Gallagher, Timothy, Brough, Paul A., Livett, Bruce G.
• Format: Article
• Language: English
• Subjects: Adrenaline release; Anabaena flos-aquae; Anatoxin-a; Animals; Bacterial Toxins - antagonists & inhibitors; Bacterial Toxins - pharmacology; Biological and medical sciences; Cattle; Cells, Cultured; Cholinergic system; Chromaffin cell; Chromaffin System - cytology; Chromaffin System - drug effects; Chromaffin System - metabolism; Cyanophyta; Epinephrine - metabolism; Marine Toxins - antagonists & inhibitors; Marine Toxins - pharmacology; Mecamylamine; Mecamylamine - pharmacology; Medical sciences; Microcystins; Neuropharmacology; Neurotoxins - antagonists & inhibitors; Neurotoxins - pharmacology; Neurotransmitters. Neurotransmission. Receptors; Nicotine - pharmacology; Nicotinic acetylcholine receptor, neuronal type; Nicotinic Agonists - pharmacology; Nicotinic receptor agonist; Noradrenaline release; Norepinephrine - metabolism; Pharmacology. Drug treatments; Potassium - pharmacology; Tropanes
• ISSN: 0922-4106; 0014-2999
• DOI: 10.1016/0922-4106(95)90153-1

(+)-Anatoxin-a is a neurotoxic alkaloid produced by the cyanobacterium Anabaena flos-aquae. In this study synthetic (±)-anatoxin-a was tested on isolated bovine adrenal chromaffin cells to determine its ability to evoke secretion of endogenous catecholamines through neuronal-type nicotinic receptor activation. Anatoxin-a was found to act as a potent agonist of the secretory response of chromaffin cells with an EC 50 of 1–2 μM, compared with an EC 50 of 4–5 μM for nicotine. The cells responded to anatoxin-a and nicotine with bell-shaped concentration-response curves consistent with desensitisation at concentrations of anatoxin-a greater than 5 μM and of nicotine greater than 20 μM. The secretion of catecholamines stimulated by anatoxin-a was completely inhibited in a non-competitive manner by the nicotinic antagonist mecamylamine with an IC 50 of 0.4–0.5 μM. In the presence of depolarising concentrations of K + (15 or 50 mM), anatoxin-a increased the secretion of catecholamines in a concentration-dependent manner up to the same maximum as that achieved by anatoxin-a alone. It is concluded that anatoxin-a acts as a potent and selective nicotinic agonist, capable of evoking secretion of endogenous catecholamines from chromaffin cells via their neuronal-type nicotinic receptor.