Two new studies reveal that the commonly used insect repellents DEET and citronellal each work through a dual stimulation of insect sensory systems. The research findings, published by Cell Press on August 26 in the journals Neuron and Current Biology, enhance our understanding of how insects respond to repellents and may lead to the discovery of improved compounds for controlling insect-borne disease.
Insect pests pose a major threat to humans across the world. In addition to spreading dreaded diseases such as malaria, insects ruin crops, causing widespread famine and starvation. Humans often try to control insects with chemical repellents. Volatile insect repellents can be applied to human skin and clothes and are detected through the insect's sense of smell, known as olfaction. Nonvolatile repellents are typically sprayed on crops and are detected via an insect's sense of taste.
In the study published in Neuron, researchers discovered that fruit flies are exquisitely sensitive to the taste of DEET. DEET has been the most common active ingredient in popular insect repellents for over fifty years, but there is some controversy over DEET's mode of action. "While it was clear that the repulsive action of DEET occurs at least in part through olfactory receptor neurons and requires an olfactory receptor called Or83b, it was not known whether DEET was also capable of acting though the sense of taste," explains senior study author, Dr. Craig Montell, from the Departments of Biological Chemistry and Neuroscience at The Johns Hopkins School of Medicine.
Dr. Montell and colleagues examined whether DEET was sensed exclusively though olfactory receptor neurons. The researchers found that DEET potently suppressed feeding behavior in fruit flies and that this effect was mediated directly by taste receptor neurons and did not involve olfactory receptor neurons. DEET activated fruit fly taste receptors that are known to be stimulated by aversive compounds, and this response was lost in flies genetically engineered to lack these specific taste receptors.
"Although DEET is definitely a volatile compound that is detected though olfactory sensory neurons, our findings demonstrate that DEET also directly activates taste receptor neurons," concludes Dr. Montell. "Thus, the effectiveness of DEET in pest control may result from its dual action in deterring insects simultaneously through both smell and taste, rather than exclusively through the olfactory response."
In the second study, published in Current Biology, Dr. Montell's group focused on how the insect olfactory system responds to citronellal, a natural insect repellent that is produced by plants. The researchers found that citronellal activated the insect's sense of smell through dual olfactory pathways. "One pathway involved the olfactory receptor, Or83b, and the other required a transient receptor potential (TRPA1) channel, which is a sentinel for avoiding other types of noxious compounds and temperatures," explains Dr. Montell. "Loss of either resulted in the same behavioral impairment but opposite cellular signaling defects."
Taken together, results from these studies reveal that two of the most effective insect repellents stimulate the insect sensory system through dual pathways. In addition, the findings may lead to development of even better repellents. "We suggest that mosquito TRPA1 represents a new potential target for screens for volatile activators that might serve as new types of insect repellents," concludes Dr. Montell.