Multiple activities of insect repellents on odorant receptors in mosquitoes

Several lines of evidence suggest that insect repellent molecules reduce mosquito-host contacts by interacting with odorants and odorant receptors (ORs), thereby ultimately affecting olfactory-driven behaviours. We describe the molecular effects of 10 insect repellents and a pyrethroid insecticide with known repellent activity on two highly specific Aedes aegypti (Diptera: Culicidae) ORs, AaOR2 + AaOR7 and AaOR8 + AaOR7, exquisitely sensitive to key mosquito attractants indole and (R)-(-)-1-octen-3-ol, expressed in oocytes of Xenopus (Anura: Pipidae). Our study demonstrates that insect repellents can both inhibit odorant-evoked currents mediated by ORs and independently elicit currents in the absence of odorants. All of the repellents had effects on one or both ORs; most of these compounds were selective inhibitors and showed a high degree of specificity in their capacity to activate the two ORs. These results show that a range of insect repellents belonging to structurally diverse chemical classes modulate the function of mosquito ORs through multiple molecular mechanisms.