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Document Type

Open Access

Degree Program

Animal Science

Degree Type

Master of Science (M.S.)

Year Degree Awarded

January 2008

Month Degree Awarded

September

Keywords

Pyrethroids, VGCC, VGClC, Synaptosomes, Rat Brain

Abstract

Select pyrethroid binary mixtures (deltamethrin plus S-bioallethrin, β-cyfluthrin, cypermethrin, and fenpropathrin) elicit a more-than-additive response on L-glutamate release from rat brain synaptosomes that is independent of calcium influx. Using a variety of chloride channel antagonists, anthracene-9-carboxylic acid (9-AC), rChlorotoxin (ClTx), 4,4’-dintitrostilbene-2,2’-disulfonic acid (DNDS), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), and picrotoxinin (PTX), we have identified two mechanisms by which pyrethroids may enhance L-glutamate release. The results from this study indicate that only ClTx and NPPB, at their EC50s (0.1 μM and 70 μM, respectively), significantly increase L-glutamate release when in the presence of our most potent pyrethroid, deltamethrin, at its EC50 (2 x 10-12 M). When these two antagonists were used in the presence of deltamethrin plus cypermethrin and deltamethrin plus fenpropathrin, a more-than-additive response was elicited at lower concentrations of the binary mixtures. Likewise, NPPB in the presence of the additive binary mixture, deltamethrin plus tefluthrin, first elicited a more-than-additive response at the 1:10 mixture. Since both ClTx and NPPB are inhibitors of voltage-gated chloride channels (ClC-2) and calcium-activated chloride channels, our findings suggest that these channels are potential target sites for certain pyrethroids and likely are important in pyrethroid neurotoxicity.

First Advisor

John M. Clark

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