靶向GABA受体的杀虫剂的作用机制、抗性和毒性

Title:Mechanisms of Action, Resistance and Toxicity of Insecticides Targeting GABA Receptors

Volume: 24 Issue: 27

关键词: polychlorocycloalkanes、烷基酚、大环内酯类、苯基异恶唑啉，，metadiamides，杀虫剂，抗性，毒性，GABA受体。

摘要: Background: γ-Aminobutyric acid (GABA) receptors play a central role in fast inhibitory neurotransmission in insects. Several classes of insecticides targeting insect GABA-gated chloride channels have been developed. The important resistant to dieldrin GABA receptor subunit (RDL) has been used to investigate insecticide sites of action using radioligands, electrophysiology and site-directed mutagenesis. Although this important subunit readily forms robust functional homomeric receptors when expressed, alternative splicing and RNA A-to-I editing can generate diverse forms of the receptor.

Methods: We have reviewed studies on native and recombinant insect GABA-gated chloride channels, their interactions with ligands acting at orthosteric and allosteric sites and their interactions with insecticides. Since some GABA receptor modulators act on L-glutamate-gated chloride channels, some comparisons are included.

Results: The actions on GABA-gated chloride channels of polychlorocycloalkanes, cyclodienes, macrocyclic lactones, phenylpyrazoles, isoxazolines, and metadiamides are described and the mechanisms of action of members of these insecticide classes are addressed. Mutations that lead to resistance are discussed as they can be important in developing field diagnostic tests. Toxicity issues relating to insecticides targeting GABA-gated chloride channels are also addressed.

An overview of all major insecticide classes targeting insect GABA-gated chloride channels has enhanced our understanding of these important receptors and their insecticide binding sites. However, the subunit composition of native GABA receptors remains unknown and studies to clarify this are needed. Also, the precise sites of action of the recently introduced isoxazolines and meta-diamides will be of interest to pursue.

Cite this article as:

Mechanisms of Action, Resistance and Toxicity of Insecticides Targeting GABA Receptors, Current Medicinal Chemistry 2017; 24 (27) . https://dx.doi.org/10.2174/0929867324666170613075736