Liu Zewen, Williamson Martin S, Lansdell Stuart J, Han Zhaojun, Denholm Ian, Millar Neil S
Department of Pharmacology, University College London, UK.
J Neurochem. 2006 Nov;99(4):1273-81. doi: 10.1111/j.1471-4159.2006.04167.x. Epub 2006 Sep 18.
Neonicotinoid insecticides are potent selective agonists of insect nicotinic acetylcholine receptors (nAChRs). Since their introduction in 1991, resistance to neonicotinoids has been slow to develop, but it is now established in some insect field populations such as the planthopper, Nilaparvata lugens, a major rice pest in many parts of Asia. We have reported recently the identification of a target-site mutation (Y151S) within two nAChR subunits (Nlalpha1 and Nlalpha3) from a laboratory-selected field population of N. lugens. In the present study, we have examined the influence of this mutation upon the functional properties of recombinant nAChRs expressed in Xenopus oocytes (as hybrid nAChRs, co-expressed with a rat beta2 subunit). The agonist potency of several nicotinic agonists has been examined, including all of the neonicotinoid insecticides that are currently licensed for either crop protection or animal health applications (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam). The Y151S mutation was found to have no significant effect on the maximal current (I(max)) observed with the endogenous agonist, acetylcholine. In contrast, a significant reduction in I(max) was observed for all neonicotinoids (the I(max) for mutant nAChRs ranged from 13 to 81% of that observed on wild-type receptors). In addition, nAChRs containing the Y151S mutation caused a significant rightward shift in agonist dose-response curves for all neonicotinoids, but of varying magnitude (shifts in EC(50) values ranged from 1.3 to 3.6-fold). The relationship between neonicotinoid structure and their potency on nAChRs containing the Y151S target-site mutation is discussed.
新烟碱类杀虫剂是昆虫烟碱型乙酰胆碱受体（nAChRs）的强效选择性激动剂。自1991年引入以来，对新烟碱类杀虫剂的抗性发展缓慢，但现在已在一些昆虫田间种群中出现，如褐飞虱，它是亚洲许多地区的主要水稻害虫。我们最近报道了在实验室选择的褐飞虱田间种群的两个nAChR亚基（Nlalpha1和Nlalpha3）中鉴定出一个靶位点突变（Y151S）。在本研究中，我们研究了该突变对非洲爪蟾卵母细胞中表达的重组nAChRs（作为与大鼠β2亚基共表达的杂交nAChRs）功能特性的影响。研究了几种烟碱激动剂的激动剂效力，包括目前用于作物保护或动物健康应用的所有新烟碱类杀虫剂（啶虫脒、噻虫胺、呋虫胺、吡虫啉、烯啶虫胺、噻虫啉和噻虫嗪）。发现Y151S突变对内源性激动剂乙酰胆碱观察到的最大电流（I(max)）没有显著影响。相比之下，所有新烟碱类杀虫剂的I(max)均显著降低（突变型nAChRs的I(max)为野生型受体观察值的13%至81%）。此外，含有Y151S突变的nAChRs使所有新烟碱类杀虫剂的激动剂剂量反应曲线显著右移，但幅度不同（EC(50)值的变化范围为1.3至3.6倍）。讨论了新烟碱类杀虫剂结构与其对含有Y151S靶位点突变nAChRs效力之间的关系。
