Mechanism of selective actions of neonicotinoids on insect nicotinic acetylcholine receptors
2005
Neonicotinoid insecticides act selectively on insect nicotinic acetylcholine receptors (nAChRs), but little is known about the mechanism of selectivity. To elucidate the mechanism, structural features of neonicotinoids and insect nAChRs contributing to this selectivity have been examined. Using molecular-oribital calculations, electrostatic interactions and hydrogen-bond formation of neonicotinoids with insect nAChRs were postulated to contribute to the selectivity of neonicotinoid-nAChR interactions. Also, the use of voltage-clamp electrophysiology combined with molecular biology showed that replacement of the vertebrate a4 subunit in the α4β2 nAChR by Drosophila a subunits and mutation to basic residues of an amino acid in loop D of the a7 nAChR enhanced neonicotinoid sensitivity of the nAChRs. These findings suggest important roles for a and non-a subunits in the selective actions of neonicotinoids on insect nAChRs.
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