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      Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

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          Abstract

          Background

          N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.

          Results

          By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.

          Conclusion

          These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

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          Most cited references36

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            Insect odorant receptors are molecular targets of the insect repellent DEET.

            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.
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              Mosquitoes smell and avoid the insect repellent DEET.

              The insect repellent DEET is effective against a variety of medically important pests, but its mode of action still draws considerable debate. The widely accepted hypothesis that DEET interferes with the detection of lactic acid has been challenged by demonstrated DEET-induced repellency in the absence of lactic acid. The most recent hypothesis suggests that DEET masks or jams the olfactory system by attenuating electrophysiological responses to 1-octen-3-ol. Our research shows that mosquitoes smell DEET directly and avoid it. We performed single-unit recordings from all functional ORNs on the antenna and maxillary palps of Culex quinquefasciatus and found an ORN in a short trichoid sensillum responding to DEET in a dose-dependent manner. The same ORN responded with higher sensitivity to terpenoid compounds. SPME and GC analysis showed that odorants were trapped in conventional stimulus cartridges upon addition of a DEET-impregnated filter paper strip thus leading to the observed reduced electrophysiological responses, as reported elsewhere. With a new stimulus delivery method releasing equal amounts of 1-octen-3-ol alone or in combination with DEET we found no difference in neuronal responses. When applied to human skin, DEET altered the chemical profile of emanations by a "fixative" effect that may also contribute to repellency. However, the main mode of action is the direct detection of DEET as indicated by the evidence that mosquitoes are endowed with DEET-detecting ORNs and corroborated by behavioral bioassays. In a sugar-feeding assay, both female and male mosquitoes avoided DEET. In addition, mosquitoes responding only to physical stimuli avoided DEET.
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                Author and article information

                Journal
                BMC Biol
                BMC Biology
                BioMed Central
                1741-7007
                2009
                5 August 2009
                : 7
                : 47
                Affiliations
                [1 ]Laboratoire de Lutte contre les Insectes Nuisibles, Institut de Recherche pour le Développement, F-34 394 Montpellier, France
                [2 ]Institute of General & Molecular Biology, N. Copernicus University, 87-100 Torun, Poland
                [3 ]Institut de Recherche pour le Développement/Centre de Recherches Entomologiques de Cotonou, 01 BP 4414, République du Bénin
                [4 ]Laboratoire Récepteurs et Canaux Ioniques Membranaires (RCIM), UPRES EA 2647/USC INRA 2023, IFR 149 QUASAV, Université d'Angers, UFR Sciences, F-49045 Angers cedex, France
                [5 ]Groupe de Biotechnologie des protéines, Université de Toulouse, Toulouse, France
                [6 ]Institute of Biochemistry, Medical Faculty, University of Ljubljana, Slovenia
                [7 ]CNRS, Institut de Neurobiologie Alfred Fessard – FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire – UPR9040, Gif sur Yvette, F-91198, France
                Article
                1741-7007-7-47
                10.1186/1741-7007-7-47
                2739159
                19656357
                37bd0e07-834b-4b69-b716-f6042c892021
                Copyright © 2009 Corbel et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2009
                : 5 August 2009
                Categories
                Research Article

                Life sciences
                Life sciences

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