title: Disruption of aminergic signalling reveals novel compounds with distinct inhibitory effects on mosquito reproduction, locomotor function and survival.
abstract: 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.
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Silke
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Pharmaco-Biology, Faculty of Pharmacy, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Ermelinda
authors.initials: E
authors.lastname: Rende
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Nolan
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000502:physiology*; D001679:Biogenic Amines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000008:administration & dosage* / Q000737:chemistry; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001679:Biogenic Amines; D007306:Insecticides