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

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 <i>Heliothis</i> 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 <i>Heliothis</i> generally parallels their inhibition of [³H]­Chlo and [³H]­Flu binding. In <i>Musca</i> 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

Insect Ryanodine Receptor: Distinct but Coupled Insecticide Binding Sites for [<i>N</i>‑C³H₃]Chlorantraniliprole, Flubendiamide, and [³H]Ryanodine

Radiolabeled anthranilic diamide insecticide [<i>N</i>-C³H₃]­chlorantraniliprole was synthesized at high specific activity. It was compared with phthalic diamide insecticide flubendiamide and [³H]­ryanodine in radioligand binding studies with house fly muscle membranes to provide the first direct evidence with a native insect ryanodine receptor that the major anthranilic and phthalic diamide insecticides bind at different allosterically coupled sites, i.e., there are three distinct Ca²⁺-release channel targets for insecticide action

Stress Response in the Honeybee (Apis mellifera L.) Gut Induced by Chlorinated Paraffins at Residue Levels Found in Bee Products

Chlorinated paraffins (CPs) have become global pollutants and are of considerable concern as a result of their persistence and long-distance transmission in the environment and toxicity to mammals. However, their risks to pollinating insects are unknown. Honeybees are classical pollinators and sensitive indicators of environmental pollution. Herein, the effects of CPs on the gut microenvironment and underlying mechanisms were evaluated and explored using Apis mellifera L. Both short- and medium-chain CPs had significant sublethal effects on honeybees at a residue dose of 10 mg/L detected in bee products but did not significantly alter the composition or diversity of the gut microbiota. However, this concentration did induce significant immune, detoxification, and antioxidation responses and metabolic imbalances in the midgut. The mechanisms of CP toxicity in bees are complicated by the complex composition of these chemicals, but this study indicated that CPs could substantially affect intestinal physiology and metabolic homeostasis. Therefore, CPs in the environment could have long-lasting impacts on bee health. Future studies are encouraged to identify novel bioindicators of CP exposure to detect early contamination and uncover the detailed mechanisms underlying the adverse effects of CPs on living organisms, especially pollinating insects