Desensitization of nicotinic acetylcholine receptors in central nervous system neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine insecticides
Desensitization of nicotinic acetylcholine receptors in central nervous system neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine insecticides
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DOI：
10.1016/j.ibmb.2011.08.001
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Salgado, Vincent L.
中科院分区：
文献类型：
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作者：
Oliveira, Eugenio E.;Schleicher, Sabine;Salgado, Vincent L.
吡虫啉、亚磺胺和两种实验用的亚磺胺类杀虫剂在粘虫体内引起以静止和虚弱为特征的一般抑郁症状，同时也不同程度地引起姿势变化，如持续的产卵器打开、腿部屈曲或伸展和腹部弯曲，这表明某些神经回路受到兴奋。我们研究了棒状昆虫神经元中烟碱型乙酰胆碱受体上的相同化合物，此前已证明，在ACh存在下，这种受体会减敏。用10(-4)M杀虫剂U型管短暂作用于1号S，诱发电流远小于ACh诱发电流，并抑制随后的ACh诱发电流数分钟，表明该化合物为低效部分激动剂，对受体有较强的脱敏作用。长时间使用低浓度杀虫剂并不能激活电流，但通过使受体脱敏而抑制ACh诱发的电流。先前描述的快速和缓慢脱敏的NACH电流I-Ach1和IACh(2)分别被发现由对杀虫剂具有不同敏感性的两种成分组成。应用吡虫啉浸浴脱敏的高敏成分I-ACh1H和I-ACh2H的IC(50)S分别为0.18和0.13 PM。它对低灵敏度的缓慢减敏组件进行减敏。I-ACh2L的IC50值为2.6 nM，而快速脱敏电流成分IACh1L的敏感性最低，IC50值为81 nM。I-ACh1L对三种磺胺类药物均不敏感，而三种磺胺亚胺均能有效地脱敏I-ACh1H和两种缓慢脱敏成分，IC(50)S在2~7 nM之间。我们得出结论，某些nAChR亚型的选择性脱敏可以解释吡虫啉和亚磺胺对粘虫的杀虫作用。(C)2011爱思唯尔有限公司。保留所有权利。
Imidacloprid, sulfoxaflor and two experimental sulfoximine insecticides caused generally depressive symptoms in stick insects, characterized by stillness and weakness, while also variably inducing postural changes such as persistent ovipositor opening, leg flexion or extension and abdomen bending that could indicate excitation of certain neural circuits. We examined the same compounds on nicotinic acetylcholine receptors in stick insect neurons, which have previously been shown to desensitize in the presence of ACh. Brief U-tube application of 10(-4) M solutions of insecticides for 1 s evoked currents that were much smaller than ACh-evoked currents, and depressed subsequent ACh-evoked currents for several minutes, indicating that the compounds are low-efficacy partial agonists that potently desensitize the receptors. Much lower concentrations of insecticides applied in the bath for longer periods did not activate currents, but inhibited ACh-evoked currents via desensitization of the receptors. Previously described fast- and slowly-desensitizing nACh currents, I-Ach1 and IAch(2) respectively, were each found to consist of two components with differing sensitivities to the insecticides. Imidacloprid applied in the bath desensitized high-sensitivity components, I-ACh1H and I-ACh2H with IC(50)s of 0.18 and 0.13 pM, respectively. It desensitized the low-sensitivity slowly desensitizing component. I-ACh2L, with an IC50 of 2.6 nM, while a component of the fast-desensitizing current, IACh1L, was least sensitive, with an IC50 of 81 nM I-ACh1L appeared to be insensitive to the three sulfoximines tested, whereas all three sulfoximines potently desensitized I-ACh1H and both slowly desensitizing components, with IC(50)s between 2 and 7 nM. We conclude that selective desensitization of certain nAChR subtypes can account for the insecticidal actions of imidacloprid and sulfoximines in stick insects. (C) 2011 Elsevier Ltd. All rights reserved.