Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management , University of California , Berkeley , California 94720 , United States.
J Agric Food Chem. 2018 Apr 4;66(13):3277-3290. doi: 10.1021/acs.jafc.7b05984. Epub 2018 Mar 21.
Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH ubiquinone oxidoreductase. Pyrethroids and other Na channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.
杀虫剂放射性配体可直接识别和分析对有效和安全害虫防治至关重要的作用靶标和作用机制。这些放射性配体或是杀虫剂本身，或是与其结合在相同或偶联部位的类似物。在昆虫和哺乳动物中，首选的放射性配体及其靶标通常是γ-氨基丁酸（GABA）受体的三氧杂环丁烷、谷氨酸受体的阿维菌素、烟碱型乙酰胆碱受体的吡虫啉、肌醇三磷酸受体的瑞诺定和氯虫苯甲酰胺、以及 NADH 泛醌氧化还原酶的鱼藤酮或哒螨灵。由于亲脂性和高非特异性结合，拟除虫菊酯和其他钠通道调节剂杀虫剂通常不是很好的放射性配体。对于靶标验证，结合测定中与放射性配体竞争的结构活性关系应该与杀虫活性或毒性相同，除了快速解毒或前杀虫剂类似物。一旦放射性配体测定法被证明具有相关性，它通常有助于在选择抗性害虫品系、昆虫和哺乳动物之间的选择性以及与调节剂位点的解毒剂和其他化学物质的相互作用方面定义靶标修饰。结合测定还可用于受体分离和光亲和标记，以表征涉及的相互作用。
