Pyrethroid insecticides indirectly inhibit GABA-dependent 36Cl − influx in synaptoneurosomes from the trout brain

Abstract

Rainbow trout ( Oncorhynchus mykiss) are extremely sensitive to the neurotoxic activity of pyrethroid insecticides. One possible target for pyrethroids is the GABA A receptor of brain of the trout, the function of which can be tested by measurement of influx of 36Cl − into synaptoneurosomes, in response to the application of agonists. γ-Aminobutyric acid produced a time- and concentration-dependent increase in influx of 36Cl − in synaptoneurosomes from the brain of the trout, which exhibited the pharmacology characteristic of a response mediated by activation of a GABA A receptor. Deltamethrin, (1RαS)- cia-cypermethrin and permethrin produced a dose-dependent increase in the basal uptake and a corresponding decrease in GABA-dependent influx, with a maximum inhibition of 70–82%. This effect of pyrethroid was stereospecific, of high potency and inhibited by tetrodotoxin (TTX) and t-butylbicy-clophosphorothionate (TBPS). The sensitivity of the effect of the pyrethroid to TTX suggested an activation by pyrethroid of the voltage-dependent sodium channel. Veratridine, a sodium channel activator, elicited similar changes in the basal uptake of chloride, which were TTX-sensitive. Neither deltamethrin nor veratridine had a measurable effect on the efflux of 36Cl − from synaptoneurosomes. Thus, pyrethroid insecticides may interfere with the function of GABA A receptors indirectly through an interaction with the voltage-dependent sodium channel in the brain of the trout and consequently perturb chloride influx, possibly through a voltage-dependent chloride channel.