title: Diamide insecticide target site specificity in the Heliothis and Musca ryanodine receptors relative to toxicity.
abstract: 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.
authors.affiliation: Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California , Berkeley, California 94720-3112, United States.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Qi
authors.forename: Peter
authors.initials: P
authors.lastname: Lümmen
authors.forename: Ralf
authors.initials: R
authors.lastname: Nauen
authors.forename: John E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D001665:Binding Sites; D003958:Diamide / Q000737:chemistry* / Q000633:toxicity; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry* / Q000633:toxicity; D009036:Moths / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D019837:Ryanodine Receptor Calcium Release Channel; D003958:Diamide
keywords: anthranilic diamides; phthalic diamides; ryanodine receptor; structure−activity relationship; toxicity