Fuchs Silke, Rende Ermelinda, Crisanti Andrea, Nolan Tony
Department of Life Sciences, Imperial College London, London, UK.
Department of Pharmaco-Biology, Faculty of Pharmacy, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
Sci Rep. 2014 Jul 2;4:5526. doi: 10.1038/srep05526.
Insecticide resistance amongst disease vectors is a growing problem and novel compounds are needed. Biogenic amines are important for neurotransmission and we have recently shown a potential role for these in mosquito fertility. Here, we dissected the relative contribution of different aminergic signalling pathways to biological processes essential for vectorial capacity such as fertility, locomotion and survival by injecting agonists and antagonists and showed that octopaminergic/tyraminergic signalling is essential for oviposition and hatching rate. We show that egg melanisation is regulated by adrenergic signalling, whose disruption causes premature melanisation specifically through the action of tyramine. In addition to this, co-injection of tyramine with DOPA, the precursor of melanin, had a strong cumulative negative effect on mosquito locomotion and survival. Dopaminergic and serotonergic antagonists such as amitriptyline and citalopram recapitulate this effect. Together these results reveal potential new target sites for the development of future mosquito sterilants and insecticides.
病媒昆虫的抗药性问题日益严重,因此需要新型化合物。生物胺对神经传递至关重要,我们最近发现它们在蚊子繁殖力方面具有潜在作用。在此,我们通过注射激动剂和拮抗剂,剖析了不同胺能信号通路对媒介能力所必需的生物学过程(如繁殖力、运动能力和生存能力)的相对贡献,并表明章鱼胺能/酪胺能信号通路对产卵和孵化率至关重要。我们发现卵黑化受肾上腺素能信号通路调节,该信号通路的破坏会通过酪胺的作用导致过早黑化。除此之外,将酪胺与黑色素前体多巴共同注射,对蚊子的运动能力和生存能力有强烈的累积负面影响。多巴胺能和5-羟色胺能拮抗剂(如阿米替林和西酞普兰)也会产生这种效果。这些结果共同揭示了未来开发蚊子绝育剂和杀虫剂的潜在新靶点。