Faculty of Life and Environmental Sciences, Shimane University, Matsue, Shimane, Japan.
Interdisciplinary Institute for Science Research, Head Office for Research and Academic Information, Shimane University, Matsue, Shimane, Japan.
Biosci Biotechnol Biochem. 2021 Jun 24;85(7):1563-1571. doi: 10.1093/bbb/zbab089.
In the late 1970s, we discovered that toxic bicyclic phosphates inhibit the generation of miniature inhibitory junction potentials, implying their antagonism of γ-aminobutyric acid (GABA) receptors (GABARs; GABA-gated chloride channels). This unique mode of action provided a strong incentive for our research on GABARs in later years. Furthermore, minor structural changes conferred insect GABAR selectivity to this class of compounds, convincing us of the possibility of GABARs as targets for insecticides. Forty years later, third-generation insecticides acting as allosteric modulator antagonists at a distinctive site of action in insect GABARs were developed. G protein-coupled receptors (GPCRs) are also promising targets for pest control. We characterized phenolamine receptors functionally and pharmacologically. Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz. Given the presence of multiple sites of action, ion channels and GPCRs remain potential targets for invertebrate pest control.
在 20 世纪 70 年代末，我们发现有毒双环膦酸盐抑制微小抑制性突触后电位的产生，这表明它们拮抗γ-氨基丁酸（GABA）受体（GABAR；GABA 门控氯离子通道）。这种独特的作用模式强烈激励了我们在随后几年对 GABAR 的研究。此外，微小的结构变化使这类化合物对昆虫 GABAR 具有选择性，这使我们相信 GABAR 有可能成为杀虫剂的作用靶点。四十年后，第三代杀虫剂作为变构调节剂拮抗剂，在昆虫 GABAR 的独特作用部位发挥作用。G 蛋白偶联受体（GPCR）也是害虫防治的有前途的靶点。我们从功能和药理学上对酚胺受体进行了表征。在所测试的受体中，β-肾上腺素样章鱼胺受体对杀螨剂/杀虫剂双甲脒最为敏感。鉴于存在多个作用部位，离子通道和 GPCR 仍然是无脊椎动物害虫防治的潜在靶点。
