Neonicotinoid insecticides display partial and super agonist actions on native insect nicotinic acetylcholine receptors
Neonicotinoid insecticides display partial and super agonist actions on native insect nicotinic acetylcholine receptors
复制标题
DOI：
10.1111/j.1471-4159.2006.04084.x
复制
发表时间：
2006-10-01
影响因子：
4.7
通讯作者：
Sattelle, David B.
中科院分区：
文献类型：
--
作者：
Brown, Laurence A.;Ihara, Makoto;Sattelle, David B.
烟碱乙酰胆碱受体（nictinic acetylcholine receptor, nAChRs）在昆虫神经组织中高密度存在，是新烟碱类杀虫剂的靶点。进一步了解这些杀虫剂的作用将有助于开发新的化合物。本研究采用全细胞膜片钳法记录了3龄果蝇幼虫中枢神经系统培养的胆碱能神经元，考察了乙酰胆碱（ACh）和尼古丁，以及新烟碱类吡虫啉、噻虫苷和p - ch-噻虫苷对这些神经元天然nachr的作用。剂量-反应数据显示，乙酰胆碱的EC50值为19 μ m。尼古丁和吡虫啉对天然乙酰胆碱受体均为低效激动剂，其最大电流振幅为乙酰胆碱受体的10-14%。相反，在相同的神经元中，clothianidin和P-CH-clothianidin引起的最大电流幅值比100 μ M ACh引起的最大电流幅值高56%。这是首次证明杀虫剂对原生昆虫nachr具有“超级”激动作用。细胞贴附记录表明，在观察到的最大电导状态（63.5 pS）下，更频繁的打开导致了超激动作用。
Nicotinic acetylcholine receptors (nAChRs) are present in high density in insect nervous tissue and are targeted by neonicotinoid insecticides. Improved understanding of the actions of these insecticides will assist in the development of new compounds. Here, we have used whole-cell patch-clamp recording of cholinergic neurons cultured from the central nervous system of 3rd instar Drosophila larvae to examine the actions of acetylcholine (ACh) and nicotine, as well as the neonicotinoids imidacloprid, clothianidin and P-CH-clothianidin on native nAChRs of these neurons. Dose-response data yield an EC50 value for ACh of 19 mu M. Both nicotine and imidacloprid act as low efficacy agonists at native nAChRs, evoking maximal current amplitudes 10-14% of those observed for ACh. Conversely, clothianidin and P-CH-clothianidin evoke maximal current amplitudes up to 56% greater than those evoked by 100 mu M ACh in the same neurons. This is the first demonstration of 'super' agonist actions of an insecticide on native insect nAChRs. Cell-attached recordings indicate that super agonism results from more frequent openings at the largest (63.5 pS) conductance state observed.