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Pyrethroid insecticide-induced alterations in mammalian synaptic membrane potential
J T Eells1, P A Bandettini, P A Holman
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
The Journal of Pharmacology and Experimental Therapeutics
|September 1, 1992
Summary
Pyrethroid insecticides, including type I and type II, activate voltage-gated sodium channels in rat brain synaptosomes. This action causes membrane depolarization and neurotransmitter release, indicating their neurotoxic mechanism.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Pyrethroids are widely used insecticides with known neurotoxic effects.
- Understanding the precise mechanism of pyrethroid neurotoxicity is crucial for risk assessment.
Purpose of the Study:
- To characterize the neuroexcitatory actions of type I and type II pyrethroids in rat brain synaptosomes.
- To investigate the effects of pyrethroids on synaptosomal membrane potential and neurotransmitter release.
Main Methods:
- Utilized [3H]tetraphenylphosphonium to measure synaptosomal membrane potential changes.
- Measured the release of [3H]acetylcholine from synaptosomes.
- Tested concentration-dependent and stereospecific effects of various pyrethroids.
Main Results:
- Both type I and type II pyrethroids caused concentration-dependent, tetrodotoxin-sensitive membrane depolarization.
- Deltamethrin was the most potent pyrethroid, followed by cypermethrin, fenvalerate, and permethrin.
- Pyrethroids increased spontaneous [3H]acetylcholine release, correlating with membrane depolarization.
Conclusions:
- Pyrethroids potently and stereoselectively target voltage-sensitive sodium channels, increasing sodium influx.
- This leads to membrane depolarization and neurotransmitter release, elucidating their neurotoxic mechanism.
- Synaptosomal membrane potential changes serve as a sensitive indicator of pyrethroid action and toxicity.