Diamide Insecticide Target Site Specificity in the Heliothis and Musca Ryanodine Receptors Relative to Toxicity

• Published in: Journal of agricultural and food chemistry 2014-05, Vol.62 (18), p.4077-4082
• Main Authors: Qi, Suzhen, Lümmen, Peter, Nauen, Ralf, Casida, John E
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Diamide - chemistry; Diamide - toxicity; Insect Proteins - chemistry; Insect Proteins - metabolism; Insecticides - chemistry; Insecticides - toxicity; Moths - chemistry; Moths - drug effects; Moths - metabolism; Ryanodine Receptor Calcium Release Channel - chemistry; Ryanodine Receptor Calcium Release Channel - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf501236h

Anthranilic and phthalic diamides act on the ryanodine receptor (RyR), which constitutes the Ca2+-activated Ca2+ channel and can be assayed as shown here in Heliothis thoracic muscle tissue with anthranilic diamide [3H]chlorantraniliprole ([3H]Chlo), phthalic diamide [3H]flubendiamide ([3H]Flu), and [3H]ryanodine ([3H]Ry). Using Heliothis with [3H]Chlo or [3H]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 [3H]Ry binding in Heliothis generally parallels their inhibition of [3H]Chlo and [3H]Flu binding. In Musca adults [3H]Ry binding site stimulation is a good predictor of in vivo activity for anthranilic but not phthalic diamides, and no high-affinity [3H]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.