Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles

WE aimed to ascertain whether pyrethroid insecticides could influence the vesicular transport of the excitatory amino acid glutamate. The incubation of rat cortical synaptic vesicles with resmethrin and permethrin, consistently 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 gradient (Delta Phi(sv)). Meanwhile, the vesicular influx of Cl-36(-) anions was impaired by pyrethroid concentrations which did not affect the ATP-dependent uptake of [C-14]methylamine, as a marker for the proton gradient (Delta pH). Thus, the stimulation of glutamate transport appeared to involve mainly the Delta Phi(sv). A self-attenuating effect of selected pyrethroids on putatively enhanced excitatory transmission in severe intoxication is suggested. (C) 1998 Lippincott Williams & Wilkins.