新型二酰胺类杀虫剂对鱼尼丁受体作用的分子机理

Molecular mechanism of action of novel diamide insecticides on ryanodine receptor

最近发现了一类新型二酰胺类杀虫剂——氟虫酰胺和氯虫酰胺,其作用靶标是鱼尼丁受体(ryanodine receptors,RyRs)。本文对RyR的结构与功能、电压门控钙离子通道和鱼尼丁受体钙离子释放通道对细胞质钙离子内环境稳定的调节以及二酰胺类杀虫剂对RyRs作用的分子机理进行综述。二酰胺类杀虫剂使昆虫RyR通道处于持续的开放状态,引发钙离子从肌质网腔内大量释放,破坏了细胞质钙离子内环境的稳定,从而产生不同的药物学特性。这些变化都是由一个不同于鱼尼丁在RyR上的结合部位介导的。该类杀虫剂的作用对昆虫RyRs是高度专一的,结果产生选择毒性。由于二酰胺类杀虫剂的结构独特,作用方式新颖,对鳞翅目害虫效果好、杀虫谱广,对各种益虫和天敌安全,并对现用的杀虫剂无交互抗性,故它们非常适合于抗性治理和IPM。

Diamide insecticide flubendiamide and ehlorantraniliprole, with ryanodine receptors （RyRs） as targets, were recently discovered. Here we reviewed the structure and function of RyR, regulation of intracellular calcium homeostasis by voltage-gated calcium channel and RyR/calcium release channel and molecular mechanisms of action of diamide insecticides on RyRs. Diamide insecticides stabilize insect RyR channels to open state, evoking massive calcium release from intracellular stores, and then disrupt the calcium homeostasis, and possess distinct pharmacological characteristics, which are mediated by a binding site different from that of ryanodine. The action of this class of insecticides is highly specific to insect RyRs and results in selective toxicity. Diamide insecticides have a unique chemical structure and a novel mode of action and show excellent efficacy, a broad insecticidal spectrum against lepidopterous insect pests, excellent safety against various beneficial arthropods and natural enemies, and no cross-resistance to existing insecticides. They will be very suitable for insecticide resistance management and IPM programs.