Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California , Berkeley, California 94720-3112, United States.
J Agric Food Chem. 2014 May 7;62(18):4077-82. doi: 10.1021/jf501236h. Epub 2014 Apr 24.
Anthranilic and phthalic diamides act on the ryanodine receptor (RyR), which constitutes the Ca(2+)-activated Ca(2+) channel and can be assayed as shown here in Heliothis thoracic muscle tissue with anthranilic diamide [(3)H]chlorantraniliprole ([(3)H]Chlo), phthalic diamide [(3)H]flubendiamide ([(3)H]Flu), and [(3)H]ryanodine ([(3)H]Ry). Using Heliothis with [(3)H]Chlo or [(3)H]Flu gives very similar anthranilic and phthalic diamide binding site structure-activity correlations, indicating a common binding site. The anthranilic and phthalic diamide stimulation of [(3)H]Ry binding in Heliothis generally parallels their inhibition of [(3)H]Chlo and [(3)H]Flu binding. In Musca adults [(3)H]Ry binding site stimulation is a good predictor of in vivo activity for anthranilic but not phthalic diamides, and no high-affinity [(3)H]Flu specific binding site is observed. These relationships establish species differences in diamide target site specificity important in structure optimization and target site-based resistance mechanisms.
邻苯二甲酰亚胺和邻苯二甲酰胺作用于肌浆网 Ca2+通道，即兰尼碱受体（RyR）。如本文所示，在 Heliothis 胸肌组织中可对 RyR 进行检测，所用方法为使用邻苯二甲酰亚胺 [(3)H]氯虫酰胺 ([(3)H]Chlo)、邻苯二甲酰胺 [(3)H]氟苯虫酰胺 ([(3)H]Flu) 和 [(3)H]ryanodine ([(3)H]Ry) 对其进行标记。使用 Heliothis 对 [(3)H]Chlo 或 [(3)H]Flu 进行标记，得到的邻苯二甲酰亚胺和邻苯二甲酰胺结合部位结构活性相关性非常相似，表明存在共同的结合部位。邻苯二甲酰亚胺和邻苯二甲酰胺对 [(3)H]Ry 结合的刺激作用通常与它们对 [(3)H]Chlo 和 [(3)H]Flu 结合的抑制作用一致。在 Musca 成虫中，[(3)H]Ry 结合部位的刺激作用是邻苯二甲酰亚胺而不是邻苯二甲酰胺体内活性的良好预测因子，并且未观察到高亲和力的 [(3)H]Flu 特异性结合部位。这些关系确立了二酰胺靶标特异性的物种差异，这在结构优化和基于靶标抗性机制中非常重要。
