Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7).
Anatoxin-a(s) is a guanidine methyl phosphate ester (unprotonated molecular ion equals 252 daltons) isolated from the freshwater cyanobacterium (blue-green alga) Anabaena flos-aquae strain NRC 525-17. Previous work has shown anatoxin-a(s) to be a potent irreversible inhibitor of electric eel acetylcholinesterase (EC 3.1.1.7, AChE). In the present study the interaction of anatoxin-a(s) with AChE was investigated by protection studies and since similarities have been noted between anatoxin-a(s) and the synthetic organophosphate anticholinesterases, the ability of reactivators to reactivate the inhibited enzyme was investigated. Treatments directed toward eliminating poisoning symptoms and in vivo protection from anatoxin-a(s) poisonings were investigated using oxime reactivators and atropine or pretreatment with a carbamate and atropine. Anatoxin-a(s) was shown to be an active site-directed inhibitor of acetylcholinesterase which is resistant to oxime reactivation due to the structure of its enzyme adduct. In vivo pretreatment with physostigmine and high concentrations of 2-PAM were the only effective antagonists against a lethal dose of anatoxin-a(s).
Hyde
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EG
Biomedical Sciences Ph.D. Program, Wright State University, Dayton, Ohio 45435.
Carmichael
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WW
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001665:Binding Sites / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D000458:Cyanobacteria / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004593:Electrophorus / Q000378:metabolism; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins; D014326:Tropanes
D001427:Bacterial Toxins; D002800:Cholinesterase Inhibitors; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; C509783:anatoxin a; D000110:Acetylcholinesterase