| 18383452 |
Clark JM, Symington SB: Neurotoxic implications of the agonistic action of CS-syndrome pyrethroids on the N-type Ca (v) 2.2 calcium channel. Pest Manag Sci. 2008 Jun;64(6):628-38.
BACKGROUND: Cismethrin (T-syndrome) and deltamethrin (CS-syndrome) pyrethroids have been previously shown to increase membrane depolarization and calcium influx, but only deltamethrin increased Ca (2+)-dependent neurotransmitter release from rat brain synaptosomes. Deltamethrin's action was blocked by omega-conotoxin GVIA, delineating a separate action at N-type Ca (v) 2.2 channels that is consistent with the in vivo release of neurotransmitter. It is hypothesized that other CS-syndrome pyrethroids will elicit similar actions at presynaptic nerve terminals. RESULTS: Nine additional pyrethroids were similarly examined, and these data were used in a cluster analysis. CS-syndrome pyrethroids that possessed alpha-cyano groups, cypermethrin, deltamethrin and esfenvalerate, all caused Ca (2+) influx and neurotransmitter release and clustered with two other alpha-cyano pyrethroids, cyfluthrin and cyhalothrin, that shared these same actions. T-syndrome pyrethroids, bioallethrin, cismethrin and fenpropathrin, did not share these actions and clustered with two non-alpha-cyano pyrethroids, tefluthin and bifenthrin, which likewise did not elicit these actions. Deltamethrin reduced peak current of heterologously expressed wild-type Ca (v) 2.2, increased peak current of T422E Ca (v) 2.2 and was 20-fold more potent on T422E Ca (v) 2.2 than on wild-type channels, indicating that the permanently phosphorylated form of Ca (v) 2.2 is the preferred target. CONCLUSIONS: Ca (v) 2.2 is directly modified by deltamethrin, but the resulting perturbation is dependent upon its phosphorylation state. The present findings may provide a partial explanation for the different toxic syndromes produced by these structurally distinct pyrethroids. |
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