Muscarinic acetylcholine receptor activation synergizes the knockdown and toxicity of GABA-gated chloride channel insecticides.
Muscarinic acetylcholine receptor activation synergizes the knockdown and toxicity of GABA-gated chloride channel insecticides.
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DOI：
10.1002/ps.7079
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发表时间：
2022-11
影响因子：
4.1
通讯作者：
Gross, Aaron D.
中科院分区：
文献类型：
--
作者：
Xie, Na;Gross, Aaron D.
害虫管理需要不断确定新的生理目标和战略，以控制影响农业和公共/动物健康的害虫。我们建议毒蕈碱系统作为农药的目标，因为它的生理重要性。与毒蕈碱系统不同，γ-氨基丁酸（GABA）受体是一种既定的杀虫剂靶标。在这里，我们研究了使用小分子探针（激动剂和拮抗剂）对毒蕈碱系统的靶点协同作用及其增强GABA能杀虫剂在果蝇（Meigen）中毒性的能力。毛果芸香碱（毒蕈碱激动剂）的口服给药增强了狄氏剂、氟虫腈和林丹的毒性，导致杀虫剂的杀虫比（SR）在4-32倍（口服给药）之间或2-67倍（局部施用）之间。毛果芸香碱和GABA杀虫剂之间的协同作用大于与阿托品（毒蕈碱拮抗剂）观察到的协同作用，并且大于或相当于与代谢抑制剂胡椒基丁醚观察到的协同作用。除了致死性之外，毛果芸香碱还增加了林丹的击倒。还使用细胞外电生理学在中枢神经系统中研究了协同作用的机制，其中毛果芸香碱（3 μ mol/L）将林奈福的半数最大抑制浓度（IC 50）从1.3氟虫腈的IC_（50）为2.2（1.54-3.29）μ mol/L ~ 0.56（0.40-0.77）μmol/L。毒蕈碱和GABA能系统之间的细胞功能的趋同通过调节中枢神经系统（CNS）来增强GABA受体阻断剂的杀虫活性。这些发现的未来影响可能是随着毒蕈碱增效剂的发展，配方中所需的活性成分减少。版权所有© 2022作者。有害生物管理科学由John Wiley & Sons Ltd代表化学工业协会出版。毒蕈碱型乙酰胆碱受体的激活与γ-氨基丁酸抑制杀虫剂一起导致增强的击倒和死亡率。昆虫神经系统内的靶点协同作用可能在昆虫害虫管理中发挥作用，并开发出选择性和有效的化学物质。
Pest management requires continual identification of new physiological targets and strategies to control pests affecting agriculture and public/animal health. We propose the muscarinic system as a target for agrochemicals because of its physiological importance. Unlike the muscarinic system, gamma‐amino butyric acid (GABA) receptors are an established insecticide target. Here, we investigated target‐site synergism using small molecule probes (agonist and antagonist) against the muscarinic system and their ability to enhance the toxicity of GABAergic insecticides in Drosophila melanogaster (Meigen). Oral delivery of pilocarpine (muscarinic agonist) enhanced the toxicity of dieldrin, fipronil, and lindane, resulting in synergist ratios (SRs) between 4–32‐fold (orally delivered) or between 2–67‐fold when insecticides were topically applied. The synergism between pilocarpine and the GABA‐insecticides was greater than the synergism observed with atropine (muscarinic antagonist), and was greater, or comparable, to the synergism observed with the metabolic inhibitor piperonyl butoxide. In addition to lethality, pilocarpine increased the knockdown of lindane. The mechanism of synergism was also investigated in the central nervous system using extracellular electrophysiology, where pilocarpine (3 μmo/L) lowered the half‐maximal inhibitory concentration (IC50) of lindane from 1.3 (0.86–1.98) μmol/L to 0.17 (0.14–0.21) μmol/L and fipronil's IC50 from 2.2 (1.54–3.29) μmol/L to 0.56 (0.40–0.77) μmol/L. Convergence of the cellular function between the muscarinic and GABAergic systems enhanced the insecticidal activity of GABA receptor blocking insecticides through the modulation of the central nervous system (CNS). The future impact of the findings could be the reduction of the active ingredient needed in a formulation with the development of muscarinic synergists. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Activation of muscarinic acetylcholine receptors in conjunction with gamma‐amino butyric acid inhibiting insecticides results in enhanced knockdown and mortality. Target‐site synergism within the insect nervous system may play a role in insect pest management with the development of selective and effective chemistries.
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DOI：
10.1523/jneurosci.0378-08.2008
发表时间：
2008-07-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dittman JS;Kaplan JM
通讯作者：
Kaplan JM
影响因子：
--
作者：
Balali-Mood, M;Shariat, M
通讯作者：
Shariat, M
影响因子：
64.8
作者：
BIGG, DCH;PURVIS, SR
通讯作者：
PURVIS, SR
影响因子：
6.1
作者：
HAYASHI, M;MATSUMURA, F
通讯作者：
MATSUMURA, F
影响因子：
1.9
作者：
CHADWICK, PR
通讯作者：
CHADWICK, PR