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  • Title: Pyrethroid insecticide-induced alterations in mammalian synaptic membrane potential.
    Author: Eells JT, Bandettini PA, Holman PA, Propp JM.
    Journal: J Pharmacol Exp Ther; 1992 Sep; 262(3):1173-81. PubMed ID: 1527722.
    Abstract:
    The neuroexcitatory actions of two toxicologically distinct classes of pyrethroid insecticides were characterized in rat brain synaptosomes using [3H]tetraphenylphosphonium to measure changes in synaptosomal membrane potential and by measuring the release of [3H]acetylcholine. Both type I (permethrin) and type II (deltamethrin, cypermethrin and fenvalerate) pyrethroids produced a concentration-dependent tetrodotoxin-sensitive membrane depolarization which was stereospecific for the neurotoxic isomer of each pyrethroid. Deltamethrin was the most potent and efficacious pyrethroid in these studies, with an EC50 of 30 nM and a maximal estimated membrane depolarization of 27 mV, followed by cypermethrin, fenvalerate and permethrin. The phenoxybenzyl pyrethroids also increased the spontaneous release of [3H]acetylcholine from rat brain synaptosomes, further supporting a depolarizing action of these insecticides on nerve terminal membranes. Pyrethroid-induced release of [3H]acetylcholine was tetrodotoxin-sensitive and occurred over the same concentration range as membrane depolarization. These data indicate that type I and type II phenoxybenzyl pyrethroids act potently and stereoselectively on the voltage-sensitive sodium channel to increase sodium influx into synaptic terminals producing membrane depolarization and neurotransmitter release. Furthermore, they show that pyrethroid-induced alterations in synaptosomal membrane potential is a sensitive measure of pyrethroid action on the sodium channel and of pyrethroid toxicity.
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