Gaba receptor insecticide non-competitive antagonists may bind at allosteric modulator sites.

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Law RJ, Lightstone FC

Gaba receptor insecticide non-competitive antagonists may bind at allosteric modulator sites.

Int J Neurosci. 2008 May;118(5):705-34. doi: 10.1080/00207450701750216.

PubMed ID

18446586 [ View in PubMed

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Abstract

Results from several studies have shown that a series of chemically distinct insecticide compounds (picrotoxin, BIDN, TBPS, fipronil, lindane, EBOB, and alpha-endosulfan) affect GABA A receptor function. In this investigation, docking of this set of insecticides to the GABA receptor identified five potential binding sites. The lowest energy site was found within the base of the transmembrane bundle, interacting with M2 but not in the pore, and includes many of the residues previously experimentally implicated in insecticide binding. Many of the binding modes are suggestive of a non-competitive allosteric mechanism based on interruption of the channel gating mechanism rather than directly blocking the channel. The results also distinguished between isomers of hexachlorohexane (HCH), where gamma-HCH (lindane) binds more favorably than beta-HCH. The results suggest multiple sites for insecticide binding and may suggest further mutagenesis and labeling work to either confirm or rule out these findings.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Picrotoxin	Gamma-aminobutyric acid receptor subunit alpha-1	Protein	Humans	Yes	Antagonist	Details
Picrotoxin	Gamma-aminobutyric acid receptor subunit rho-1	Protein	Humans	Yes	Antagonist	Details