Scientists at the Rockefeller University have stumbled upon what they believe to be a better explanation of the ability of N,N-diethyl-meta-toluamid's (DEET) to repel insects from skin. In A Natural Polymorphism Alters Odour and DEET Sensitivity in an Insect Odorant Receptor, an article appearing in the Sept., 21, 2011, edition of Nature, the researchers suggest that the compound interferes with smell-sensing neurons in insect antennae.
According the article, DEET has been previously reported to either affect an insect's gustatory receptors to act as a chemorepellent or to affect an insect's olfactory system. Neither of these explanations truly explains the mechanism, according to the team. Therefore, they suggested that DEET scrambles the messages in an insect's neurons about the odors surrounding them, making them less effectively attracted to their target.
The researchers recorded the electrical activity of four olfactory neurons in the fruitfly Drosophila melanogaster, which is also affected by DEET. The chemical alone barely triggered the neurons, but when the researchers combined it with 10 different odors, they saw that DEET sometimes inhibited neuron activity, sometimes enhanced it and sometimes had no effect at all. This showed the researchers that the chemical confused the insect rather than disgusting it.
The researchers suggest that DEET functions as a modulator of the odor-gated ion channel formed by the insect odorant receptor complex. The functional insect odorant receptor complex consists of the common co-receptor (ORCO) and one or more variable odorant receptor subunits that confer odor selectivity. DEET acts on this complex to inhibit odor-evoked activity or to inhibit odor-evoked suppression of spontaneous activity. This modulation depends on the specific odorant receptor and the concentration and identity of the odor ligand.
A member of research team, which was led by Leslie Vosshall, hypothesized that natural strains of Drosophila might show different sensitivities to DEET, and started screening strains from around the world. Only 18 strains later, the scientists identified one from Brazil that was not affected by DEET, although its responses to odors were otherwise normal.
The team found that an odorant receptor (OR59B) on the olfactory neurons in the insensitive flies differs from the receptors in sensitive strains by just one amino acid, but they think this is enough to make the flies insensitive to DEET. This showed the researchers that DEET can directly interact with odorant receptors.
Because their research focused on Drosophilia, it may not directly explain the mechanism behind repelling mosquitos. The team would like to find a new chemical that is safer and can be used at lower doses. They are now screening chemical libraries for such molecules to find one that shuts down the mosquito's olfactory system, and they reportedly have some leads.