Anatoxin-a interactions with cholinergic synaptic molecules.
Anatoxin-a, a bicyclic amine isolated from blue-green alga, binds to the nicotinic acetylcholine receptor of Torpedo electric tissue, thereby inducing conformational changes in the postsynaptic receptor--ion channel complex as evidenced by alterations in the binding of radiolabeled ligands to the complex. Anatoxin-a binds to the acetylcholine recognition site (Kd = 0.1--0.2 microM) as indicated by its competitive inhibition of specific [3H]acetylcholine and d-[3H]tubocurarine binding, Anatoxin-a stimulates the binding of three physiologically identified "ion channel blockers," [3H]perhydrohistrionicotoxin, [3H]phencyclidine, and [3H]phencyclidine methiodide. The 50% effective doses for these effects range from 0.14 to 0.28 microM. Incubation of Torpedo membranes with anatoxin-a before addition of a radiolabeled channel probe produces a time- and concentration-dependent attenuation of the binding compared to the situation in which anatoxin-a and the probe are added simultaneously. The time course for the elaboration of this decrease corresponds to electrophysiological measurements of anatoxin-a-induced desensitization of neuromuscular junction responses. In these nicotinic actions, anatoxin-a is about as potent as acetylcholine. Anatoxin-a has relatively low affinity for the muscarinic acetylcholine receptors of rat brain, inhibiting 3-[3H]quinuclidinyl benzilate binding (10(-10) M) by 50% at concentrations between 10 and 20 microM. In contrast to classical muscarinic agonists, anatoxin-a displays little regional selectivity in its binding, and its receptor affinity is unaltered by alkylation of the neural membranes with N-ethylmaleimide.
D000818:Animals; D001427:Bacterial Toxins; D001665:Binding Sites; D001921:Brain / Q000187:drug effects*; D000087522:Cyanobacteria Toxins; D007473:Ion Channels / Q000187:drug effects*; D008387:Marine Toxins / Q000494:pharmacology*; D052998:Microcystins; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014101:Torpedo; D014326:Tropanes
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D007473:Ion Channels; D008387:Marine Toxins; D052998:Microcystins; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014326:Tropanes; C509783:anatoxin a