If you have scratched a mosquito bite, then you have experienced one itchy consequence of the mosquito’s sensitive sense of smell, known as olfaction.
Mosquitos and other insects use special odor-sensing nerve cells (olfactory neurons) in their antennae to find egg-laying sites and blood meal sources. Channels in the olfactory neurons, called odorant receptors, bind to smell-causing chemicals known as odorants. Once the channel binds and responds to an odorant, the neuron signals to the brain that an attractive or repulsive scent is close by.
In collaboration with their University of Florida colleagues, Gregory M. Pask and Laurence J. Zwiebel at Vanderbilt University showed in research published in the journal Chemical Senses this month that the drug amiloride and closely related compounds can block olfactory receptor responses in insects.
“This paper identifies new chemical tools that people in insect olfaction research can use to study olfactory receptors better. A lot of the tools that are out there now are generic channel blockers,” said Pask. The work, funded by the NIH, gives scientists studying insect olfaction more specific ways to block olfactory receptors to better study how they work. Understanding mosquito odorant receptor function could decrease the spread of disease by discovering ways to prevent mosquitos from smelling and detecting humans as blood meal sources.
In the study, Pask and his co-authors treated cells, possessing an insect odorant receptor and a necessary co-receptor on their surfaces, with some of the thousands of drugs from a chemical compound library. By inserting a tiny electrode into the cells, they measured changes in current, which represent the cell’s response to the chemicals.
When the team exposed the cells to a known activating compound (the agonist), they observed a typical, high activation response. When they used the agonist and added amiloride or one of its more efficient family members, however, the cells showed an unusually low activation response. The data suggest that these compounds block the ability of the odorant receptor to respond to odorants. If the channel cannot respond, the neuron will not signal to the bug’s brain about important smells nearby.
So are amiloride-like compounds going to show up in your bug spray? “The issue with these molecules is they’re not volatile [able to be vaporized], so you couldn’t cover yourself with them,” said Pask. “At this point, their main use is in basic research and understanding how odorant receptors work.”
In terms of the global health impacts of understanding insect olfaction, Pask said, “The mosquito uses its olfactory system to locate not only human hosts, but also where a good site is to lay their eggs and where to find flowers and fruits for nectar feeding. If you could block their ability to sense these things, they would have to rely on other pathways to find the things they need.”
Manipulating mosquito olfaction could have extraordinary effects on human health. According to the Bill & Melinda Gates Foundation, mosquito-borne malaria kills almost 1 million people per year. Dengue virus, also transmitted by mosquitos, requires hospitalization for approximately 500,000 people per year, as reported by the World Health Organization. Mosquito saliva carries and passes both the malaria parasite and dengue virus to people during blood meals.
The influence of amiloride on insect olfaction research extends beyond global health. Olfaction plays a large role in crop damage caused by insects. Pask’s research showed that odorant receptors from agricultural pests (western tarnished plant bug and tobacco budworm, a moth) are also blocked by amiloride and related compounds.
“The agricultural component is huge as far as moth pests. Usually it’s not the adult moths that are destructive; it’s the moth larvae. So if you can control where they lay their eggs, then you can push them away from your crop,” Pask said. Insect olfaction is essential in female choice of egg-laying sites. Using amiloride family members to study olfaction in this context may therefore have positive agricultural implications.
So what comes next in studying insect olfaction? It turns out that odorant receptors are not the only receptors that contribute to olfaction. “There is also another set of receptors called the IRs,” Pask said. IR stands for ionotropic receptor, and the role of IRs in insect olfaction is not well understood. Though little is known about IRs, the amiloride compound family has the potential to block their function, further demonstrating the power of this new tool for understanding insect olfaction in the future.