Phthalic acid diamides receptors

In sununary, phthalic acid diamides increased the ryanodine affinity of the Heliothis ryanodine receptor. At low [Ca ] the compounds offset the cooperativity between the ryanodine sites. 

Phthalic Acid Diamides Elicited Calcium Release Mediated by Ryanodine Receptors... 

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. 

Secondly, the calcium transients were sensitive to inhibition by ryanodine, but they were not affected by the IP3R blocker xestospongine (18 19). Consequently, it was concluded that the ryanodine receptor was the target site of phthalic acid diamides. 

Phthalic Acid Diamides Increased the Ryanodine Affinity of Ryanodine Receptors... 

Equilibrium binding of [ H]ryanodine to Heliothis flight muscle microsomes clearly revealed cooperativity between the binding sites at 100 pM [Ca ]. Based on the assumption that RyRs are arranged in arrays of calcium release units in insect as well as in mammalian sarcpplasmic reticulum membranes (22), a plausible explanation would be that ryanodine receptors opened by calcium may have activated adjacent RyR channels by intermolecular interactions. Phthalic acid diamides completely converted the receptors to the high-affinity conformation as revealed by the hyperbolic binding iso erm. 

Besides their importance as potent insecticides, phthalic acid diamides, a new class of allosteric ryanodine receptor effectors, may be used as novel pharmacological tools in the functional and structural characterization of this fascinating ion channel. 

---