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Title:   Author  item
                                            Bohbot, Jonathanitem
                                            FU, L - National Institutes Of Health (NIH)item
                                            Le, Thanhitem
                                            Chauhan, Kamleshitem
                                            Cantrell, Charlesitem
                                            Dickens, Joseph
  Submitted to: Medical and Veterinary Entomology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/4/2011
                                    Publication  Date: 3/13/2011
                                    Citation: Bohbot, J.D., Fu, L., Le, T.N., Chauhan, K.R., Cantrell, C.L., Dickens, J.C. 2011. Multiple activities of insect repellents on odorant receptors in mosquitoes. Medical and Veterinary Entomology. dx.doi.org/10.1111/j.1365-2915.2011.00949.x.Interpretive Summary: Mosquitoes are the most dangerous animals on earth. Each year several million people die as a result of mosquito-vectored diseases. Insect repellents may be used to decrease contact between disease-vectoring mosquitoes and their animal or human hosts; thus, decreasing the liklihood of disease transmission. However, the mechanisms by which repellents have their effects are disputed and poorly understood. Here we demonstrate that 11 insect repellents including an insecticide with known repellent activity have multiple effects on two key odor receptors for attractants in the yellow fever mosquito. This study supports a previous report by us on the mode of action of insect repellents. These results will be used by chemists and pharmacologists as the basis for discovery of novel or enhanced repellents, or combinations of repellents based on their differential effects on specific odor receptors.
                                Technical Abstract: Several lines of evidence suggest that insect repellent molecules reduce mosquito-host contacts by interacting with odorants and odorant receptors (ORs) ultimately affecting olfactory-driven behaviors. We describe the molecular effects of ten insect repellents and a pyrethroid insecticide with known repellent activity on two highly specific Aedes aegypti ORs, AaOR2+AaOR7 and AaOR8+AaOR7, exquisitely sensitive to key mosquito attractants, indole and (R)-(-)-1-octen-3-ol, expressed in Xenopus oocytes. 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.


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