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Differential Actions of Fipronil and Dieldrin Insecticides on GABA-Gated Chloride Channels in Cockroach Neurons
Abstract
Fipronil and dieldrin are known to inhibit GABA receptors in both mammals and insects. However, the mechanism of selective toxicity of these insecticides between mammals and insects remains to be seen. One possible mechanism is that insect GABA receptors are more sensitive than mammalian GABAA receptors to fipronil and dieldrin. We examined differential actions of fipronil and dieldrin on GABA-gated chloride channels in insects and compared them with the data on mammalian GABAA receptors. Neurons were acutely dissociated from the American cockroach thoracic ganglia, and currents evoked by GABA were recorded by the whole-cell patch-clamp technique. GABA-evoked currents were carried by chloride ions, blocked by picrotoxinin, but not by bicuculline. Fipronil inhibited GABA currents with an IC50 value of 28 nM, whereas dieldrin exhibited a dual action potentiation with an EC50 value of 4 nM followed by inhibition with an IC50 value of 16 nM. Fipronil and dieldrin acted on the resting receptor at comparable rates, whereas fipronil blocked the activated receptor 10 times faster than dieldrin. Fipronil inhibition was partially reversible, whereas dieldrin inhibition was irreversible. Fipronil was 59 times more potent on cockroach GABA receptors than on rat GABAA receptors. However, the potentiating and inhibitory potencies of dieldrin in cockroach GABA receptors were comparable with those in rat GABAA receptors. It was concluded that the higher toxicity of fipronil in insects than i…
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Metadata
- Authors
- Zhao, X., Salgado, V. L., Yeh, J. Z., & Narahashi, T.
- Affiliations
- Northwestern University (US)
- Bayer (Germany) (DE)
- ORCID
- Salgado, Vincent L.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 306
- Issue
- 3
- Pages
- 914-924
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2150646988
- Cited by
- 125
- References
- 48
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 15 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Thoracic Society
- National Institute of Neurological Disorders and Stroke (NS-14143, R01NS014143)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pesticide Exposure and Toxicity
- Keywords
- fipronil, dieldrin, insecticide selectivity, GABA-gated chloride channels, GABAA receptor, cockroaches, Periplaneta americana, insecticidal mechanism, receptor potentiation, receptor inhibition, irreversible inhibition, picrotoxinin, bicuculline, neurotoxicity
- MeSH terms
- Animals, Cockroaches, Dieldrin, gamma-Aminobutyric Acid, Insecticides, Neurons, Pyrazoles, Receptors, GABA, Chloride Channels
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