Department of Chemistry, University of California, Berkeley , California 94720-1460, United States.
Chem Res Toxicol. 2013 Apr 15;26(4):514-6. doi: 10.1021/tx400055p. Epub 2013 Mar 12.
The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB) binding to house fly head membranes with an IC50 of 0.2 nM in a manner characteristic of GABA-gated chloride channel antagonists. To further define its mode of action, we prepared phenyl-labeled [(3)H]A1443 as described with a specific activity of 14 Ci/mmol. This new radioligand with an apparent IC50 of about 0.4 nM is poorly displaced by most insecticides acting at the [(3)H]EBOB site. Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA/glutamate chloride channel activator site. These findings revive interest in the insect GABA/glutamate receptor as an insecticide target.
高效且选择性的异噁唑啉类杀虫剂 A1443 以其特征性方式强力置换 [(3)H] 炔基二环辛酯 ([(3)H]EBOB) 与家蝇头部膜的结合，其 IC50 为 0.2 nM，是 GABA 门控氯离子通道拮抗剂。为了进一步确定其作用模式，我们按照描述用苯基标记了 [(3)H]A1443，其比活度为 14 Ci/mmol。这种新的放射性配体的表观 IC50 约为 0.4 nM，与大多数在 [(3)H]EBOB 位点起作用的杀虫剂的置换能力较差。有趣的是，异噁唑啉结合位点直接与阿维菌素 GABA/谷氨酸氯离子通道激活剂位点偶联。这些发现重新激发了人们对昆虫 GABA/谷氨酸受体作为杀虫剂靶标的兴趣。
