Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles

WE aimed to ascertain whether pyrethroid insecticides could influence the v esicular transport of the excitatory amino acid glutamate. The incubation o f rat cortical synaptic vesicles with resmethrin and permethrin, consistent ly stimulated both ATP-dependent and -independent uptake of [H-3]glutamate, while not evoking depletion of its vesicular content. Both processes were counteracted by valinomycin, a dissipator of the transmembrane potential gr adient (Delta Phi(sv)). Meanwhile, the vesicular influx of Cl-36(-) anions was impaired by pyrethroid concentrations which did not affect the ATP-depe ndent uptake of [C-14]methylamine, as a marker for the proton gradient (Del ta pH). Thus, the stimulation of glutamate transport appeared to involve ma inly the Delta Phi(sv). A self-attenuating effect of selected pyrethroids o n putatively enhanced excitatory transmission in severe intoxication is sug gested. (C) 1998 Lippincott Williams & Wilkins.