Ryanodine activation, flubendiamide

Therefore it was concluded that flubendiamide acts as a selective activator of the insect ryanodine receptor, inducing ryanodine-sensitive cytosolic Ca transients. Furthermore, radioligand binding studies using microsomal membranes from Heliothis flight muscles demonstrated that flubendiamide allosterically increased the ryanodine affinity. Flubendiamide was found to bind to Heliothis microsomal membranes with an apparent of 4.7 nM. Known ryanodine receptor ligands such as cyclic ADP-ribose, caffeine, ryanodine, and dantrolene did not interfere... 

New agrochemicals introduced in the past five years include new chemistries with known modes of action, such as the protoporphyrinogen inhibitor bencarba-zone, the phytoene desaturase picolinafen and beflutamid, and sodium channel pyrethroids new chemistries with possibly new modes of action, such as flonic-amid and pyridalyl and new chemistries with established new modes of actions, such as flubendiamide, which activates ryanodine-sensitive intracellular calcium release channels, ryanodine receptors RyR, in insects. 

DuPont has also introduced a new class of insecticides, the anthranilic diamides, such as DP-23 [205], which, like flubendiamide, also act by activating the ryanodine receptor [206],... 

Calcium channels (ryanodine receptor) Ryanodine, flubendiamide, chlorantraniliprole Activation... 

Flubendiamide is most effective on larvae followed by adults, but it has no ovicidal activity. In the course of extensive research on the mode of action of flubendiamide, it was determined that flubendiamide was a ryanodine receptor modulator. Flubendiamide Axes the Ca-channel of insect ryanodine receptors (RyR) in the open state, and subsequently induces calcium release from the membrane vesicle... 

Flubendiamide is a novel insecticide possessing potent and selective activity against lepidopterous insects [1], This insecticidal activity has been clarified to be mediated by a ryanodine-sensitive calcium release channel (RyR) [2-3], The stabilization of RyR to open state by the compound induces robust calcium release from intracellular calcium store (Figure 1). This implies a significant impact on components involved in intracellular calcium homeostasis such as the pump, a pivotal component which reuptakes released Ca into SR. In this study, we examined effects on the Ca pump, as a consequence of the calcium mobilization induced by flubendiamide. 

Figure 3. Effect of flubendiamide, ryanodine, and caffeine on the Ca -ATPase activity of the membrane preparation [3],...

Flubendiamide, a novel insecticide, selectively activates lepidopterous ryanodine receptor (S. Kiyonaka, Kyoto Univ., Japan)... 

The current study shows that phthalic acid diamide insecticides, represented by flubendiamide and its sulfoxide analogue, activated ryanodine receptors present in isolated Heliothis neurons, as concluded from the following results. Firstly, calcium transients evoked by phthalic acid diamides were independent of the extracellular [Ca ], in contrast to the signals elicited by acetylcholine. This was interpreted as calcium release from intracellular stores of the endo(sarco)plasmic reticulum, which could in principle be mediated by two different release channels, namely the ryanodine receptor and the IP3 receptor. 

It is noteworthy that the inactivation of the Heliothis RyR at millimolar [Ca ] was prevented at all flubendiamide concentrations tested. This could plausibly explain the insecticidal mechanism since deactivation of calcium release channels at high [Ca ] would be essential to terminate the intracellular calcium transient (27). According to this hypothesis, ryanodine receptors would be fixed in the (sub)conductance conformation leading to calcium store depletion and, possibly, to subsequent activation of capacitative calcium entry through plasma membrane channels. This would override compensatory calcium removal mechanisms such as the sarcoplasmic Ca-ATPase (SERCA) activity and the sodium-calcium exchanger (NCX) in the plasma membrmie. The sustained high intracellular [Ca would finally lead to muscle contraction paralysis that is consistently observed in flubendiamide-affected lepidopteran larvae. 

Flubendiamide Selectively Activated Insect ryanodine Receptors... 

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