UC Riverside researchers say they have found the long-sought receptors in mosquitoes that are affected by DEET, the most common active ingredient used in popular insect repellents.

Identifying the receptors, they say, could lead to more effective and less annoying chemicals for deterring mosquitoes, as well as other insect pests. One compound they’ve identified so far is a grape extract that, unlike DEET, doesn’t damage plastic and nylon.

Anandasankar Ray, an associate professor of entomology and the study’s director, said the discovery opens new doors for dealing with mosquito-borne illness as well as other insect-related problems, possibly even as treatments for agricultural crops. Finding better ways to keep the insects at bay is important worldwide, where mosquito-borne diseases kill hundreds of thousands of people every year.

In recent years, Ray’s lab has made other mosquito discoveries, such as finding ways to block a mosquito’s ability to detect carbon dioxide, the primary method it uses to find human or animal prey.

This most recent work, he said, “is certainly as important if not, potentially, more important than our earlier discovery.”

DEET was developed in the 1940s by the U.S. military. Armed services personnel were being sent to tropical regions wherer mosquitoes spread illnesses such as malaria and yellow fever. But the exact mechanism that made DEET effective remained a mystery.

It is not used much in developing countries where mosquitoes carry illnesses that infect millions annually; the chemical is too expensive and requires frequent application.

“Scientists had been unable to figure how mosquitoes can detect DEET vapors,” Ray said. “Without knowing the protein receptors that activate the insect repellent pathways, it was very difficult to design substitutes for DEET that are better.”

While it is an effective repellent — estimates are that one-third of Americans use a DEET containing product — it can be a skin irritant. It also can damage some plastics and nylon, Ray said.

He and his team found the DEET receptors by using a protein that causes nerve cells to fluoresce green when stimulated. The researchers placed fruit flies — which have the same antennae receptors as mosquitoes — in confined tubes where their only sensory stimulation was from DEET. They then dissected the insects, looking for nerve cells with the tell-tale fluorescent green.

Such receptors usually are found on the hairs extending from the antennae. These, however were imbedded inside the antennae, in a little-studied structure called the sacculus. “That is perhaps why others had missed it,” Ray said.

Once they found the receptors, the researchers began looking for other materials that would stimulate the nerve cells in the same way as DEET does. Using a computer model that was able to suggest similar compounds, they screened half a million chemicals.

“We were able to find 1,000 predicted new repellents,” Ray said. From those, they identified 150 that were natural compounds. “We realized we could find some that were pleasant-smelling and affordable,” he said. “We purchased 10 of these, and eight turned out to be strong repellents.”

They ran complete tests on half of those, three of which already are widely used in food manufacturing as flavorings and are derived from common fruits. The advantage of such chemicals, Ray said, is that they are already FDA approved and will not require extensive testing.

Ray already helped launch one Riverside company that is manufacturing wearable patches that block a mosquito’s ability to detect carbon dioxide; now he is exploring the potential for another company to work on commercializing a new repellent.

Because insects have so many similarities, he said, the repellents could be effective on other insects such as agricultural pests.

“For plant pests, if we can make it work, that would be quite a big breakthrough,” he said.

“That has not been made yet, but it opens the door.”

Mosquito Facts

Species worldwide: About 3,500

Diseases spread: Malaria, West Nile virus, encephalitis, yellow fever, dengue fever

Malaria toll: Millions of people infected annually; 660,000 deaths estimated in 2011

Prey location: Mosquitoes are attracted by odor, temperature, carbon dioxide; documented preference for beer drinkers.

Food: Only females consume blood; both sexes eat nectar and other plant sugars.

Breeding: Water required, since that’s where eggs are laid.

Lifespan: 2 weeks to 6 months

Bites: Red, itchy bump is an allergic reaction to female’s anticoagulant saliva.

Scary fact: One mosquito species, found on all continents except Antarctica, can carry a disease called “chikungunya” which means “that which bends over.” It causes joint pain so severe it leaves people unable to stand or even sit up for weeks or months. The disease has been spreading from Africa into Southeast Asia, and it has shown up in Italy. “A widespread population of Asian tiger mosquitoes combined with globe-trotting humans means that chikungunya can arrive in the United States at any time,” according to a June 2011 article on Smithsonian.com.