Nature2013-10-26 1:40 AM

Odour receptors and neurons for DEET and new insect repellents 避蚊胺和驱虫剂的气味感受器和神经元

Abstract There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure–activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a+ neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide. 论文摘要 DEET,即N,N-二甲基间甲苯酰胺(N,N-diethyl-m-toluamide)和驱虫剂的嗅觉受体和神经元 由于还未明确造成嗅觉排斥的具体受体,想要找到改进的DEET替代品有诸多主要的阻碍。测试新的化学品是否对人体使用安全需要花费昂贵的成本。本文中我们识别出了黑腹果蝇触角一组小坑样结构内叫做球囊的神经元对DEET敏感。他们表达了高度保守的受体,Ir40a蛋白受体,和那些神经元被抑制或Ir40a蛋白受体被抑制的蝇类失去了对DEET的驱避作用。我们对超过40万化合物的结构活性进行计算机算法筛选,确认了其中过百种自然化合物作为候选驱避剂,测试了其中多数后发现他们中的大部分能激活Ir40a+神经元且是对果蝇的驱避剂。这些化合物也是对蚊子的强力驱避剂。那些不含有能溶解塑料的化学物质的候选驱虫剂物美价廉且气味温和,具有类似葡萄的芳香,其中三种已确定对人类食品是安全的。我们的研究发现为研发新一代有力对抗全球范围内致命虫媒传染疾病的驱虫剂铺平了道路。

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