Binary mixtures of pyrethroids produce differential effects on Ca influx and glutamate release at isolated presynaptic nerve terminals from rat brain |
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Authors: | Steven B Symington Hilliary E HodgdonRichard K Frisbie J Marshall Clark |
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Institution: | a Department of Biology and Biomedical Science, Salve Regina University, Newport, RI 02840, USA b Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA c Molecular & Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA |
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Abstract: | 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 EC50s with deltamethrin always as one of the two components, cismethrin, λ-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 λ-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. |
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Keywords: | Pyrethroids Binary mixtures Voltage-sensitive calcium channels Voltage-sensitive sodium channels Voltage-sensitive chloride channels Glutamate release Calcium influx Presynaptic nerve terminals Rat brain Synaptosomes |
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