Binary mixtures of pyrethroids produce differential effects on Ca2+ influx and glutamate release at isolated presynaptic nerve terminals from rat brain

Isolated rat brain synaptosomes were used to evaluate the action of pyrethroid mixtures on Ca2+ influx and subsequent glutamate release under depolarizing conditions. In equipotent binary mixtures at their respective and/or estimated EC(50)s with deltamethrin always as one of the two components, cismethrin, lambda-cyhalothrin, cypermethrin, esfenvalerate and permethrin were additive and S-bioallethrin, fenpropathrin and tefluthrin were less-than-additive on Ca2+ influx. In binary mixtures with deltamethrin always as one of the two components, esfenvalerate, permethrin and tefluthrin were additive and lambda-cyhalothrin was less-than-additive on glutamate release. Binary mixture of S-bioallethrin and cismethrin was additive for both Ca2+ influx and glutamate release. Only a subset of pyrethroids (S-bioallethrin, cismethrin, cypermethrin, and fenpropathrin) in binary mixtures with deltamethrin caused a more-than-additive effect on glutamate release. These binary mixtures were, however, only additive (cismethrin and cypermethrin) or less-than-additive (S-bioallethrin and fenpropathrin) on Ca2+ influx. Therefore, increased glutamate release evoked by this subset of pyrethroids in binary mixture with deltamethrin is not entirely occurring by Ca2+-dependent mechanisms via their action at voltage-sensitive calcium channels. These results suggest that pyrethroids do not share a common mode of toxicity at presynaptic nerve terminals from rat brain and appear to affect multiple target sites, including voltage-sensitive calcium, chloride and sodium channels. (C) 2010 Elsevier Inc. All rights reserved.