Anatoxin-a is a potent agonist of the nicotinic acetylcholine receptor of bovine adrenal chromaffin cells.
(+)-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 EC50 of 1-2 microM, compared with an EC50 of 4-5 microM 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 microM and of nicotine greater than 20 microM. The secretion of catecholamines stimulated by anatoxin-a was completely inhibited in a non-competitive manner by the nicotinic antagonist mecamylamine with an IC50 of 0.4-0.5 microM. 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.
Molloy
L
L
Department of Biochemistry, University of Melbourne, Parkville, VIC, Australia.
Wonnacott
S
S
Gallagher
T
T
Brough
P A
PA
Livett
B G
BG
D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004837:Epinephrine / Q000378:metabolism; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008464:Mecamylamine / Q000494:pharmacology; D052998:Microcystins; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D014326:Tropanes
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D009498:Neurotoxins; D018722:Nicotinic Agonists; D014326:Tropanes; D008464:Mecamylamine; D009538:Nicotine; C509783:anatoxin a; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine