Molecular mechanism of selective toxicity of neonicotinoids

Actions of neonicotinoids on wild-type and mutant alpha 7 nicotinic receptors were investigated using voltage-clanip electrophysiology to elucidate the mechanism underlying the selectivity of neonicotinoids to insect nicotinic acetylcholine receptors. It was found that when neonicotinoids bind to the receptor, the nitro group is located close to loops D and F, which was supported by the models of the agonist binding domain of the alpha 7 nicotinic receptor. Structural features of Drosophila D alpha 2 subunit involved in interactions with imidacloprid were also studied using chimeras as well as mutant alpha subunits. The results suggested that the region loop B to the N-terminus. along with loop C, contributes to the selective interactions. (c) Pesticide Science Society of Japan.