Trace amines inhibit insect odorant receptor function through antagonism of the co-receptor subunit.
Trace amines inhibit insect odorant receptor function through antagonism of the co-receptor subunit.
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DOI：
10.12688/f1000research.3825.1
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Luetje CW
中科院分区：
文献类型：
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作者：
Chen S;Luetje CW
许多昆虫的行为是由嗅觉驱动的，这使得昆虫嗅觉受体(ORs)成为昆虫控制的靶标。昆虫OR是气味门控的离子通道，每个受体被认为由一个大的、可变的气味结合亚基家族的代表和一个高度保守的共受体亚单位(ORCO)组成，组装在未知的化学计量比中。最近发现了合成Orco导向的激动剂和拮抗剂。一些Orco拮抗剂已被证明是通过变构机制来抑制或激活气味的。由于Orco在昆虫物种中的高度保守性，导致Orco拮抗剂在各种昆虫的ORs上具有广泛的活性，并表明Orco配体的结合部位可能作为昆虫内源化合物的调节部位，也可能是外源化合物的靶标，例如植物产生的化合物。为了验证这一想法，我们筛选了一系列生物胺和示踪胺，鉴定出几种Orco拮抗剂。特别令人感兴趣的是色胺，一种植物产生的胺，以及酪胺，一种昆虫神经系统内源性的胺。色胺被发现是Orco的一种强有力的拮抗剂，能够阻断Orco激动剂对Orco的激活，并能变构地抑制气味物质对ORs的激活。Tyramine的效果与色胺相似，但效力较弱。最重要的是，色胺和酪胺都显示出广泛的活性，抑制来自三个不同昆虫目(双翅目、鳞翅目和鞘翅目)的ORO的气味激活，以及来自同一物种的六种不同ORO的气味激活(人类疟疾媒介蚊子，我们的结果表明，内源和外源天然化合物作为Orco配体调节昆虫的嗅觉，Orco可能是开发新型驱虫剂的重要靶标。
Many insect behaviors are driven by olfaction, making insect olfactory receptors (ORs) appealing targets for insect control. Insect ORs are odorant-gated ion channels, with each receptor thought to be composed of a representative from a large, variable family of odorant binding subunits and a highly conserved co-receptor subunit (Orco), assembled in an unknown stoichiometry. Synthetic Orco directed agonists and antagonists have recently been identified. Several Orco antagonists have been shown to act via an allosteric mechanism to inhibit OR activation by odorants. The high degree of conservation of Orco across insect species results in Orco antagonists having broad activity at ORs from a variety of insect species and suggests that the binding site for Orco ligands may serve as a modulatory site for compounds endogenous to insects or may be a target of exogenous compounds, such as those produced by plants. To test this idea, we screened a series of biogenic and trace amines, identifying several as Orco antagonists. Of particular interest were tryptamine, a plant-produced amine, and tyramine, an amine endogenous to the insect nervous system. Tryptamine was found to be a potent antagonist of Orco, able to block Orco activation by an Orco agonist and to allosterically inhibit activation of ORs by odorants. Tyramine had effects similar to those of tryptamine, but was less potent. Importantly, both tryptamine and tyramine displayed broad activity, inhibiting odorant activation of ORs of species from three different insect orders (Diptera, Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs from a single species (the human malaria vector mosquito, Anopheles gambiae). Our results suggest that endogenous and exogenous natural compounds serve as Orco ligands modulating insect olfaction and that Orco can be an important target for the development of novel insect repellants.