title: 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. gamma-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 GABAA receptor. Deltamethrin, (1R alpha S)-cis-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-butylbicyclophosphorothionate (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 GABAA 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.
authors.affiliation: College of Pharmacy, Oregon State University, Corvallis 97331.
authors.forename: A J
authors.initials: AJ
authors.lastname: Eshleman
authors.forename: T F
authors.initials: TF
authors.lastname: Murray
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002713:Chlorine / Q000378:metabolism*; D003864:Depression, Chemical; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D012474:Salmon / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides; D009419:Nerve Tissue Proteins; D009570:Nitriles; D011722:Pyrethrins; C017160:cypermethrin; C017180:decamethrin; D013779:Tetrodotoxin; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; D014701:Veratridine