Health & Medicine

Peppers a hot topic in medical research at UC Davis

Humans love Sriracha sauce, and the pleasurable, painful sensation that makes us want to slather tacos, rice and barbecue with it and other spicy condiments comes down to one molecule: capsaicin.

Professors Jie Zheng and Vladimir Yarov-Yarovoy at UC Davis, in collaboration with researchers in China, recently got an unprecedented, close-up view of this molecule, as well as what happens inside our bodies when we eat the spicy foods that contain it.

Cracking the code on how this spice affects the body could do more than satisfy culinary curiosity: It could help scientists design medication for a broad array of ailments, such as those related to cardiac dysfunction, neurological disorders and chronic pain.

“We can eventually use this method in the future to design new, more selective drugs that would have less side effects for patients,” Yarov-Yarovoy said. “That’s where we’re going.”

Humans are the only species in the world that intentionally seek out the enjoyable pain of spiciness.

When we eat hot foods, capsaicin comes into contact with our body’s primary sensor for heat and pain, which produces the sensation of spiciness.

That sensor is in fact a type of ion channel, a protein in our bodies that opens, almost like a gate, in response to a stimulus. Different ion channels respond to things such as heat, a drug or a naturally occurring compound, and their opening regulates almost all of our bodily processes, including muscle movement, heartbeats and the formation of memories. This rapid ion channel opening eventually leads to a movement in our body or a sensation that we can perceive.

“People have known for many, many years that capsaicin works on this channel to open it, but there is no structural understanding of how capsaicin binds to it and how capsaicin opens the channel,” said Fan Yang, a post-doctoral researcher in Zheng’s lab.

To determine why capsaicin causes the sensation of spiciness, researchers created a video based on computational modeling of the tiny, atomic interactions between capsaicin and the channel it interacts with.

“The capsaicin molecule in the binding pocket is not staying there stationary,” Zheng said. “In fact, a part of the molecule, the tail as we call it, is waving about like seaweed in water. If the tail is waving about, it is just like when you take a picture of somebody who is moving. You get a fuzzy picture, and we had a fuzzy picture of capsaicin.”

Results from this work help explain why capsaicin from hot peppers causes a burning sensation, but sweet peppers do not. The chemical compound in sweet peppers, called capsiate, has an oxygen where capsaicin has a nitrogen. This chemical difference, although small, determines how our heat sensor reacts. On the Scoville scale for chemicals, which measures pungency of spicy foods, capsiate has a rating of 16,000 Scoville heat units, while capsaicin comes in 10 times stronger.

The study also helps elucidate why humans are sensitive to capsaicin, but other species, such as birds, are insensitive. In fact, humans are the only species in the world that intentionally seek out the enjoyable pain of spiciness.

Capsaicin’s spiciness provides a protective element to pepper plants, but if this protection were extended to birds, it would stop birds from helping to spread its seeds. Birds have the same ion channel that we do, but there are small differences where capsaicin interacts, meaning that birds do not feel spiciness like we do.

Ion channel dysfunction is related to diseases of the heart, brain, muscles and other essential components of our body, meaning that this work may help pave the way for more effective medications that treat a variety of ailments.

A number of drugs exert their effects by interacting with ion channels. The epilepsy medication carbamazepine (Tegretol) influences an ion channel in the brain, while the anti-arrhythmic drug flecainide (Tambocor) targets an ion channel in the heart. The commonly administered drug lidocaine (Lidoderm) behaves as an anesthetic by blocking a specific ion channel related to pain.

Structural modeling done in the Yarov-Yarovoy and Zheng labs, which is allowing us to visualize the ion channels as never before, is focused on developing new, effective drugs for ion channels like those already approved.

“Even though there are a lot of details that we still need to figure out, we start to see the picture, and this is the most beautiful thing to us,” Zheng said.

Katie L. Strong: (916) 321-1101, @katielstrong

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