title: Insect odorant receptors are molecular targets of the insect repellent DEET.
abstract: DEET (N,N-diethyl-meta-toluamide) is the world's most widely used topical insect repellent, with broad effectiveness against most insects. Its mechanism of action and molecular target remain unknown. Here, we show that DEET blocks electrophysiological responses of olfactory sensory neurons to attractive odors in Anopheles gambiae and Drosophila melanogaster. DEET inhibits behavioral attraction to food odors in Drosophila, and this inhibition requires the highly conserved olfactory co-receptor OR83b. DEET inhibits odor-evoked currents mediated by the insect odorant receptor complex, comprising a ligand-binding subunit and OR83b. We conclude that DEET masks host odor by inhibiting subsets of heteromeric insect odorant receptors that require the OR83b co-receptor. The identification of candidate molecular targets for the action of DEET may aid in the design of safer and more effective insect repellents.
authors.affiliation: Laboratory of Neurogenetics and Behavior, Rockefeller University, 1230 York Avenue, Box 63, New York, NY 10065 USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ditzen
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellegrino
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Vosshall
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D003671:DEET / Q000378:metabolism / Q000494:pharmacology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004594:Electrophysiology; D005247:Feeding Behavior / Q000187:drug effects; D005502:Food; D007302:Insect Repellents / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D009154:Mutation; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D018035:Receptors, Odorant / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D029721:Drosophila Proteins; D007302:Insect Repellents; D008024:Ligands; C492465:Orco protein, Drosophila; D018035:Receptors, Odorant; D003671:DEET