Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels.
Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels.
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DOI：
10.1371/journal.pone.0064905
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Piermarini PM
中科院分区：
文献类型：
--
作者：
Raphemot R;Rouhier MF;Hopkins CR;Gogliotti RD;Lovell KM;Hine RM;Ghosalkar D;Longo A;Beyenbach KW;Denton JS;Piermarini PM
疟疾和登革热等蚊媒疾病对全球健康造成了巨大损失。用于控制蚊子的主要化学制剂是针对神经系统的杀虫剂。然而，蚊子种群中出现抗药性正在降低现有杀虫剂的效力。因此，开发新的杀虫剂迫在眉睫。在这里，我们展示了VU573，一种哺乳动物内向整流钾(KIR)通道的小分子抑制剂，抑制从埃及伊蚊(AeKir1)肾小管克隆的KIR通道(AeKir1)。将VU573注入成年雌性蚊血淋巴(Ae.埃及伊蚊)以与AeKir1通道阻滞剂一致的方式干扰尿液的产生和排泄，并在24小时内使蚊子丧失行动能力(无法飞行或死亡)。此外，VU573对蚊子的毒性(Ae.当血淋巴中钾水平升高时，埃及伊蚊(Aegypti)的情况会加剧，这表明KIR通道对于维持全动物钾的动态平衡是必不可少的。我们的研究表明，肾功能衰竭是一种很有前途的灭蚊作用机制，并促使人们发现选择性的蚊子KIR通道小分子抑制剂作为杀虫剂。
Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of Aedes aegypti (AeKir1). Injection of VU573 into the hemolymph of adult female mosquitoes (Ae. aegypti) disrupts the production and excretion of urine in a manner consistent with channel block of AeKir1 and renders the mosquitoes incapacitated (flightless or dead) within 24 hours. Moreover, the toxicity of VU573 in mosquitoes (Ae. aegypti) is exacerbated when hemolymph potassium levels are elevated, suggesting that Kir channels are essential for maintenance of whole-animal potassium homeostasis. Our study demonstrates that renal failure is a promising mechanism of action for killing mosquitoes, and motivates the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides.
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影响因子：
5.6
作者：
Raphemot R;Lonergan DF;Nguyen TT;Utley T;Lewis LM;Kadakia R;Weaver CD;Gogliotti R;Hopkins C;Lindsley CW;Denton JS
通讯作者：
Denton JS
影响因子：
11.8
作者：
Asidi A;N'Guessan R;Akogbeto M;Curtis C;Rowland M
通讯作者：
Rowland M
影响因子：
3.8
作者：
Piermarini PM;Rouhier MF;Schepel M;Kosse C;Beyenbach KW
通讯作者：
Beyenbach KW
影响因子：
3.6
作者：
Bhave, Gautam;Chauder, Brian A.;Denton, Jerod S.
通讯作者：
Denton, Jerod S.
DOI：
10.1152/ajprenal.2000.279.4.f747
发表时间：
2000-10-01
影响因子：
4.2
作者：
Masia, R;Aneshansley, D;Beyenbach, KW
通讯作者：
Beyenbach, KW