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

Amy J. Eshleman, Thomas F. Murray

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Rainbow trout (Oncorhynchus mykiss) are extremely sensitive to the neurotoxic activity of pyrethroid insecticides. One possible target for pyrethroids is the GABAA 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 GABAA 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 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.

Original languageEnglish
Pages (from-to)1333-1341
Number of pages9
JournalNeuropharmacology
Volume30
Issue number12
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint

Pyrethrins
Trout
Insecticides
gamma-Aminobutyric Acid
Tetrodotoxin
Brain
GABA-A Receptors
Veratridine
Sodium Channels
Oncorhynchus mykiss
Sodium Channel Agonists
Chlorides
Permethrin
Aminobutyrates
Chloride Channels
Pharmacology

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Pyrethroid insecticides indirectly inhibit GABA-dependent 36Cl- influx in synaptoneurosomes from the trout brain. / Eshleman, Amy J.; Murray, Thomas F.

In: Neuropharmacology, Vol. 30, No. 12, 1991, p. 1333-1341.

Research output: Contribution to journalArticle

@article{d8832c2414ec4e8b92c6b8032e0026b8,
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 GABAA 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 GABAA 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 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.",
author = "Eshleman, {Amy J.} and Murray, {Thomas F.}",
year = "1991",
doi = "10.1016/0028-3908(91)90031-6",
language = "English",
volume = "30",
pages = "1333--1341",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Pyrethroid insecticides indirectly inhibit GABA-dependent 36Cl- influx in synaptoneurosomes from the trout brain

AU - Eshleman, Amy J.

AU - Murray, Thomas F.

PY - 1991

Y1 - 1991

N2 - Rainbow trout (Oncorhynchus mykiss) are extremely sensitive to the neurotoxic activity of pyrethroid insecticides. One possible target for pyrethroids is the GABAA 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 GABAA 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 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.

AB - Rainbow trout (Oncorhynchus mykiss) are extremely sensitive to the neurotoxic activity of pyrethroid insecticides. One possible target for pyrethroids is the GABAA 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 GABAA 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 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.

UR - http://www.scopus.com/inward/record.url?scp=0025995486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025995486&partnerID=8YFLogxK

U2 - 10.1016/0028-3908(91)90031-6

DO - 10.1016/0028-3908(91)90031-6

M3 - Article

VL - 30

SP - 1333

EP - 1341

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 12

ER -