Pharmacological characterization of cis‐nitromethylene neonicotinoids in relation to imidacloprid binding sites in the brown planthopper, Nilaparvata lugens

Abstract

Neonicotinoid insecticides, such as imidacloprid, are selective agonists of the insect nicotinic acetylcholine receptors (nAChRs) and extensively used in areas of crop protection and animal health to control a variety of insect pest species. Here we describe that two cis-nitromethylene neonicotinoids (IPPA152002 and IPPA152004), recently synthesized in our laboratory, discriminated between the high and low affinity imidacloprid binding sites in the brown planthopper, Nilaparvata lugens, a major insect pest of rice crops in many parts of Asia. [(3)H]imidacloprid has two binding sites with different affinities (Kd value of 0.0035 +/- 0.0006 nM for the high-affinity site and 1.47 +/- 0.22 nM for the low-affinity site). Although the cis-nitromethylene neonicotinoids showed low displacement ability (Ki values of 0.15 +/- 0.03 microM and 0.42 +/- 0.07 microM for IPPA152002 and IPPA152004, respectively) against [(3)H]imidacloprid binding, low concentrations (0.01 microM) of IPPA152002 completely inhibited [(3)H]imidacloprid binding at its high-affinity site. In Xenopus oocytes co-injected with cRNA encoding Nlalpha1 and rat beta2 subunits, obvious inward currents were detected in response to applications of IPPA152002 and IPPA152004, although the agonist potency is reduced to that of imidacloprid. The previously identified Y151S mutation in Nlalpha1 showed significant effects on the agonist potency of IPPA152002 and IPPA152004, such as a 75.8% and 70.6% reduction in Imax, and a 2.4- and 2.1-fold increase in EC(50). This data clearly shows that the two newly described cis-nitromethylene neonicotinoids act on insect nAChRs and like imidacloprid, discriminated between high and low affinity binding sites in N. lugens native nAChRs. These compounds may be useful tools to further elucidate the pharmacology and nature of neonicotinoid binding sites.

Investigating the mode of action of sulfoxaflor: a fourth‐generation neonicotinoid

“…The fact that TMX followed the trend of all the other neonicotinoids is further evidence that TMX has a bona fide nAChR binding site, as previously demonstrated . IMD is known to have two distinct binding sites in hemipteran insects: a sub‐nM‐affinity but low‐abundance site and a low‐nM‐affinity site at higher abundance . The fact that the sulfoxaflor binding site is present at relatively low abundance (in a B max range similar to that of the sub‐nM site of IMD) and is displaced at p M concentrations by IMD is highly suggestive that sulfoxaflor is selectively interacting at the high‐affinity IMD nAChR binding site.…”

“…33 IMD is known to have two distinct binding sites in hemipteran insects: a sub-nM-affinity but low-abundance site and a low-nM-affinity site at higher abundance. 8,27,36 The fact that the sulfoxaflor binding site is present at relatively low abundance (in a B max range similar to that of the sub-nM site of IMD) and is displaced at pM concentrations by IMD is highly suggestive that sulfoxaflor is selectively interacting at the high-affinity IMD nAChR binding site. This would explain why sulfoxaflor is relatively weak in [ 3 H]-IMD displacement studies, where the tracer ligand is present at a concentration in which occupancy at both sites can be expected.…”

Pleiotropic Effects of Loss of the Dα1 Subunit in Drosophila melanogaster: Implications for Insecticide Resistance

“…Mutations in the orthologs of Da3 and Db1 have been identified in neonicotinoid-resistant strains of Nilaparvata lugens (Liu et al 2005) and Myzus persicae (Bass et al 2011), respectively. While only one imidacloprid-binding site has been reported in adult D. melanogaster and other Dipteran and Lepidopteran species (Tomizawa and Casida 1997;Lind et al 1998), multiple binding sites have been reported in several Hemipteran species (Lind et al 1998;Xu et al 2010;Bass et al 2011). Unlike Hemipterans, Dipterans and Lepidopterans are holometabolous insects that undergo complete metamorphosis from larva to adult.…”

The mode of action of a nitroconjugated neonicotinoid and the effects of target site mutation Y151S on its potency

“…Unfortunately, the activities of these compounds had no superiority over imidacloprid. But the bioassay showed that an imidacloprid resistant strain of N. lugens was with less cross-resistance to these cis-neonicotinoids, when compared to imidacloprid itself or other trans-neonicotinoids (Shao et al, 2008;Xu et al, 2010). These results implied the further structural modification to keep the cis-configuration of the eNO 2 or eCN group might give valuable results in resistance management.…”

“…The excellent activity of IPPA152201 and low cross-resistance in the imidacloprid resistant populations make it to be a potential choice. After the commercialization of the first cis-neonicotinoid (IPPA152004; Jiangsu Kwin Group Co., Ltd., China; Xu et al, 2010), it is hopeful to develop more insecticides from cis-neonicotinoids, including the nitroconjugated neonicotinoids reported in the present study.…”