Characterization of 11 commercial pyrethroids on the functional attributes of rat brain synaptosomes |
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Authors: | Steven B Symington J Marshall Clark |
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Institution: | a Department of Biology and Biomedical Sciences, Salve Regina University, Newport, RI 02840, USA b Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA c Department of Veterinary and Animal Sciences, University of Massachusetts, Morrill 1 N311B, 639 North Pleasent Street, Amherst, MA 01003, USA |
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Abstract: | The action of 11 commercial pyrethroids on Ca2+ influx and glutamate release was assessed using high-throughput functional assays with rat brain synaptosomes to better understand the mechanistic nature of pyrethroid-induced neurotoxicity and aid in the reassessment of pyrethroids in vivo. Concentration-dependent response curves for each of the non-cyano and α-cyano containing pyrethroids were determined and the data used in a cluster analysis. The previously characterized α-cyano pyrethroids that induce the CS-syndrome (cypermethrin, deltamethrin, and esfenvalerate) increased Ca2+ influx and glutamate release, and clustered with two other α-cyano pyrethroids (β-cyfluthrin and λ-cyhalothrin) that shared these same actions. Previously characterized T-syndrome pyrethroids (bioallethrin, cismethrin, and fenpropathrin) did not share these actions and clustered with two other non-cyano pyrethroids (tefluthrin and bifenthrin) that likewise did not elicit these actions. Our current findings indicate that pyrethroids that have an α-cyano group (with the exception of fenpropathrin) were more potent enhancers of Ca2+ influx and glutamate release under depolarizing conditions than pyrethroids that did not possess this functional group. The collective data set does not support the hypothesis that pyrethroids, as a class, act in a similar fashion at presynaptic nerve terminals. |
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Keywords: | Pyrethroids Synaptosomes Ca2+ influx Glutamate release Voltage-sensitive calcium channel |
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