Researchers have discovered the exact structure of the receptor that makes our sensory nerves tingle when we eat sushi garnished with wasabi. And because the “wasabi receptor” is also involved in pain perception, knowing its shape should help pharmaceutical companies develop new drugs to fight pain.
The receptor, which scientists call TRPA1, is “an important molecule in the pain pathway,” says David Julius, a professor of physiology at the University of California, San Francisco and an author of a paper published in this week’s Nature. “A dream of mine is that some of the work we do will translate into medicines people can take for chronic pain.”
Julius led a team that discovered the receptor about a decade ago. Since then, researchers have shown that TRPA1 receptors begin sending distress signals to the brain whenever they encounter pungent chemical irritants, including not only wasabi but tear gas and air pollution from cars or wood fires.
The receptors also become activated in response to chemicals released by the body itself when tissue becomes inflamed from an injury or a disease like rheumatoid arthritis.
But Julius wanted to know what the receptor looked like at the level of atoms — something that would tell him a lot about how it worked. And one day, in the hallway near his lab, he ran into Yifan Cheng, a biochemist who is an expert in single particle electron cryomicroscopy, which uses an electron microscope to study biological samples at very low temperatures.
For a long time, the technique produced only fuzzy images of structures as small as the wasabi TRPA1 receptor. “But in the last few years, this technique has undergone a revolutionary leap forward,” Cheng says.
So the researchers decided to give it a try on TRPA1, and it worked. “The big advance here is that we can actually see the structure of the molecule — we can see the atoms in the molecule,” Julius says.
That allowed the team to create a precise, three-dimensional, structural model of the receptor. The model shows how the receptor opens a channel to the nerve cell’s interior and sends a distress signal to the brain when exposed to certain chemicals.
Drug companies have already begun experimenting with medicines meant to reduce pain by blocking the receptor’s normal response. “What the structure does is, it gives pharmaceutical firms sort of a map for either tweaking the drugs that they have,” Julius says, “or for developing drugs that might have different properties.”
Drugs that affect TRPA1 receptors are desirable because they work in a different way than do existing pain relievers, Julius says. And because TRPA1 receptors are highly concentrated in the nerve fibers involved in pain sensation, he says, the new drugs would be less likely to produce side effects like addiction or stomach problems.
Drugs that block the wasabi receptor might also offer a new way to treat chronic, debilitating itch, says Diana Bautista of the University of California, Berkeley. Bautista’s lab has found strong evidence that TRPA1 triggers itch sensations associated with eczema and certain nerve disorders.
“Chronic itch is very prevalent,” she says. “It’s thought to affect about 10 percent of people worldwide, and there are very few effective treatments for it.”
Bautista says drug companies are beginning to look into TRPA1 drugs as a new approach.
AUDIE CORNISH, HOST:
An update now on the science of sushi. Researchers in San Francisco have discovered the exact structure of the molecule that makes your nerves tingle when you eat sushi garnished with wasabi. And NPR’s John Hamilton says this finding has a serious side. It could help millions of people who suffer from chronic pain or itching.
JOHN HAMILTON, BYLINE: There are many kinds of pain. We can tell a burn from a slap because heat and pressure activate different tiny receptors on our sensory nerves. And one of those receptors specializes in the type of pain caused by chemical irritants, including that famous green paste. Nearly a decade ago, David Julius at the University of California San Francisco led a team that identified the wasabi receptor.
DAVID JULIUS: Well, it’s called a wasabi receptor because it’s the molecule that allows us to sort of feel that tingle.
HAMILTON: Julius says it also responds to some other pungent pain-inducing substances, including tear gas.
JULIUS: And what we’ve learned is that it’s activated by a number of environmental irritants, compounds called acrolein, which are produced by burning vegetation or in vehicle exhaust.
HAMILTON: It’s even activated by substances produced by our own bodies in response to an injury or arthritis. But Julius wanted to know what the receptor looked like at the level of atoms, something that would tell him a lot about how it worked. One day in the hallway near his lab, he ran into Yifan Cheng, a biochemist who is an expert in something called single particle electron cryo microscopy. Cheng says for a long time, the technology only produced fuzzy images of structures as small as the wasabi receptors.
YIFAN CHENG: But in the last few years, this technique has undergo a revolutionary leap forward.
HAMILTON: So the researchers decided to give it a try, and Julius says it worked.
JULIUS: The big advance here is that, you know, we can actually see the structure of the molecule where we can see the atoms in the molecule.
HAMILTON: That meant they were able to create a precise, three-dimensional model of the receptor. It shows four joined parts, each resembling a cluster of confetti streamers. Julius says the model should help drug makers, who are already developing pain relievers that work by blocking the wasabi receptor.
JULIUS: What the structure does is it gives pharmaceutical firms sort of a map for either tweaking the drugs that they have or for developing drugs that might have different properties.
HAMILTON: Existing pain drugs often have side effects. Julius says wasabi receptors make a good target because they are highly concentrated in the nerve fibers involved in pain sensation.
JULIUS: And that raises the hope that if you target them with drugs, they’ll have very selective actions.
HAMILTON: So they could relieve pain from chronic conditions like arthritis without being addictive or causing stomach problems. Diana Bautista at the University of California Berkeley says her lab began studying the wasabi receptor’s role in pain several years ago.
DIANA BAUTISTA: And since then, we’ve discovered that it plays a key role in both acute and chronic itch.
HAMILTON: Bautista says this includes itching so intense that it keeps people from sleeping or forces them to pull their car off the road so they can scratch. She says causes range from allergies, to eczema, to nerve disorders.
BAUTISTA: Chronic itch is very prevalent. It’s thought to affect about 10 percent of people worldwide, and there are very few effective treatments for it.
HAMILTON: Bautista says drugs that target the wasabi receptor could change that. And drug companies are beginning to look into the approach. But she says the new understanding of the wasabi receptor isn’t just about drug development. It’s about understanding how our sensory nerves respond to things we touch or inhale or eat.
BAUTISTA: I definitely have a much better high-resolution image of what’s happening at a molecular level when I eat wasabi.
HAMILTON: And feel that familiar tingle. The new research appears in the journal Nature. John Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.