Effects of the α subunit on imidacloprid sensitivity of recombinant nicotinic acetylcholine receptors
Effects of the α subunit on imidacloprid sensitivity of recombinant nicotinic acetylcholine receptors
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DOI：
10.1038/sj.bjp.0701618
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发表时间：
1998-02-01
影响因子：
7.3
通讯作者：
Sattelle, DB
中科院分区：
文献类型：
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作者：
Matsuda, K;Buckingham, SD;Sattelle, DB
1吡虫啉是一种对昆虫比脊椎动物具有选择性毒性的新型杀虫剂。将重组(α4β2)鸡神经元烟碱型乙酰胆碱受体(AChRs)和由黑腹果蝇神经元α亚基(SAD)与鸡β2亚基共表达形成的杂交烟碱型AChR基因在非洲爪哇卵母细胞中进行了异源表达。用双电极电压钳技术比较了吡虫啉和其他烟碱型AChR配体((+)-表巴替丁、(-)-烟碱和乙酰胆碱)对两种重组烟碱型AChR的激动剂作用。2在4种激动剂中，吡虫啉单独表现为α4β2受体的部分激动剂：(+)-表巴替丁、(-)-尼古丁和乙酰胆碱均为或接近全激动剂。吡虫啉也是杂交果蝇SAD鸡β2受体的部分激动剂，(-)-尼古丁也是，而(+)-表巴替丁和乙酰胆碱是完全激动剂。3用果蝇SADα亚基取代鸡α4亚基，降低了吡虫啉的EC50。这种α亚基替换还导致(+)-表巴替丁、(-)-尼古丁和乙酰胆碱的EC50增加。因此，果蝇(SAD)α亚基有助于吡虫啉对重组昆虫更强的表观亲和力：脊椎动物烟碱型AChRs。4吡虫啉作为SADβ2杂合受体介导的ACh反应的弱拮抗剂和α4β2受体介导的ACh反应的弱增强剂，这表明吡虫啉对这些重组受体具有复杂的影响，至少部分由α亚基决定。
1 Imidacloprid is a new insecticide with selective toxicity for insects over vertebrates. Recombinant (alpha 4 beta 2) chicken neuronal nicotinic acetylcholine receptors (AChRs) and a hybrid nicotinic AChR formed by co-expression of a Drosophila melanogaster neuronal alpha subunit (SAD) with the chicken beta 2 subunit were heterologously expressed in Xenopus oocytes by nuclear injection of cDNAs. The agonist actions of imidacloprid and other nicotinic AChR ligands ((+)-epibatidine, (-)-nicotine and acetylcholine) were compared on both recombinant nicotinic AChRs by use of two-electrode, voltage-clamp electrophysiology.2 Imidacloprid alone of the 4 agonists behaved as a partial agonist on the alpha 4 beta 2 receptor: (+)-epibatidine, (-)-nicotine and acetylcholine were all full, or near full, agonists. Imidacloprid was also a partial agonist of the hybrid Drosophila SAD chicken beta 2 receptor, as was (-)-nicotine, whereas (+)-epibatidine and acetylcholine were full agonists.3 The EC50 of imidacloprid was decreased by replacing the chicken alpha 4 subunit with the Drosophila SAD alpha subunit. This alpha subunit substitution also resulted in an increase in the EC50 for (+)-epibatidine, (-)-nicotine and acetylcholine. Thus, the Drosophila (SAD) alpha subunit contributes to the greater apparent affinity of imidacloprid for recombinant insect:vertebrate nicotinic AChRs.4 Imidacloprid acted as a weak antagonist of ACh-mediated responses mediated by SAD beta 2 hybrid receptors and as a weak potentiator of ACh responses mediated by alpha 4 beta 2 receptors, This suggests that imidacloprid has complex effects upon these recombinant receptors, determined at least in part by the alpha subunit.