Interactions of charatoxins and nereistoxin with the nicotinic acetylcholine receptors of insect cns and Torpedo electric organ

Interactions of charatoxin (4‐methylthio‐1,2‐dithiolane; ChTX) and four openchain analogs as well as nereistoxin (NTX) with acetylcholine (ACh) receptors were studied using biochemical assays on the Torpedo electric organ and honey bee brain receptors and using electrophysiological assays on the response of the cell body of the fast coxal depressor motoneuron (D_f) of the cockroach Periplaneta americana to ACh. The actions of ChTXs were complex. Except for ChTX Xl, they all potentiated the ACh‐induced current in Periplaneta neurons, but at higher concentrations all ChTXs, except for ChTX XII, caused voltage‐dependent block of this current. All CHTXs inhibited binding of [³H]perhydrohistrionicotoxin in the presence of ACh to the highaffinity noncompetitive blocker site on the Torpedo receptor, but all, except for ChTX XI, potentiated its binding in absence of ACh. The actions of ChTXs on the honey bee brain receptor were quite different from those on the Torpedo receptor. They inhibited, or had no effect on, [¹²⁵I]α‐bungarotoxin (α‐BGT) binding to the Torpedo receptor, but all ChTXs, except for ChTX I, potentiated its binding to the honey bee receptor. It is suggested that the action of ChTXs on nicotinic ACh‐receptors resulted from binding to lowaffinity noncompetitive blocker site. On the other hand, NTX was more potent than ChTXs on nicotinic ACh‐receptors, and some similarities were noted between the actions of NTX on Torpedo and honey bee receptors NTX had a weak agonistlike effect in both cases and possibly bound to the ACh binding sites as well as the high‐affinity noncompetitive blocker site. Thus the mechanisms of action of ChTXs and NTX on nicotinic ACh‐receptors are different, and there are also differences in the responses to these toxins between receptors of insect central nervous system and Torpedo electric organ.