Friday , February 3 2023

Nobel Prize in Medicine: “We need to study the components of inflammatory juice”


(EFE) .- Days after he was recognized with the Nobel Prize in Medicine for his findings on the perception of heat and cold, Professor David Julius explains in an interview with Efe the importance of studying all components of “the inflammatory soup” that it helps to warn the body of injuries.

Julius, professor and chairman of the Department of Physiology at the University of California, San Francisco (UCSF), was announced last week as the winner alongside his colleague from Scripps Research Ardem Patapoutian for his discoveries of temperature and touch receptors.

In the late 1990s, Julius’ lab identified the TRPV1 protein, a member of what are known as TRP channels (transient potential receptors) responsible for detecting intense heat such as hot peppers or chili, and later the TRPM8 protein, which does the same for the cold.

In the late 1990s, Julius’ lab identified the protein TRPV1, a member of the so-called TRP channels that detect heat, and later the protein that does the same with cold.

Question. Why are TRP channels important? What would have happened to our humans if we did not have these receptors?

Answer. It’s hard to say. It is a very broad family of molecules that perform functions, ranging from the uptake of calcium into cells to the perception of pain. There are people who have mutations in TRPV4, which is important for bone development, and therefore have skeletal or nervous system defects. What I can say is that if someone missed all the TRP channels, that person would be dead.

P. What if only TRPV1 and TRPM8 (the two identified by Julius and observing heat and cold) are missing?

R. That what I can say is that if we remove these receptors from laboratory mice, they will not die. They have deficiencies, but they live, albeit in a highly controlled environment. These receptors play a role in detecting changes in temperature, so what would happen is that you would have trouble knowing what the ambient temperature is, but not your body temperature.

P. Is that something that has been experimented with?

R. Yes. When a person is given medications that block TRP channels, they have a hard time detecting anything that is hot. This worries pharmaceutical companies, who do not want anyone to burn themselves with, for example, a coffee that is too cold, because they no longer perceive it sensually.

P. That we can live without feeling pain?

R. There are people with mutations in other types of molecules that make them unable to perceive pain stimulation. When they are small, you have to be very careful and watch over them, but if they come through that phase and learn what things they need to take care of, even if they do not feel pain, they can live a pretty good life. When the molecules we have studied are removed, only some components of pain are removed, so it is not a dramatic deficiency.

If the molecules we have studied are removed, only some components of pain are removed, so there is no dramatic deficiency

P. And are these molecules present in all animals?

R. In general, yes.

P. How are the molecules to observe the temperature (TRPV1 and TRPM8)?

R. We always describe them as a donut on the cell membrane. They are at the end of a sensory nerve in the skin like tongue, for example, and have the shape of a small donut. Under normal temperature conditions, the donut hole is closed, but when they come in contact with something called cold, the TRP channel is activated and the hole becomes larger.

P. What then goes through that hole?

R. Calcium and sodium ions enter the cell through the hole, and generate electrical currents that go to the neurons and that is when we react and say, “I’m burned!” or “How cold is this!”

P. And what is that good for us?

R. One of the main functions of pain is to tell us when we are hurting ourselves so that we can protect that area. Let’s imagine we go to the beach and burn our skin. Then the back becomes inflamed and it becomes very sensitive to changes in temperature, so when we shower with hot water, it gives us the feeling that we are burning. What this tells us is that this part of the body is injured and that we need to protect it until it is healed.

What this tells us is that that part of the body is injured and that we need to protect it until it is healed.

P. In addition to heat, TRPV1 also reacts upon contact with acid. Why?

R. Heartburn is, like heat, another component of what we call “the inflammatory soup”. It is an agent that contributes to inflammation to increase the sensitivity of that part of the body when an injury has occurred. It is very important to study all the ingredients in this “soup” to make medicines that are effective in reducing pain without blocking basic functions, such as the perception of heat and thus preventing people from burning without noticing it.

P. You started your research with the chemical compound capsaicin, found in hot peppers like chili. Why did you choose this particular connection?

R. We chose capsaicin because we wanted to study pain in general. Chili is a product whose herbs have long been used as medicine, and we knew that capsaicin is a very powerful activator of the nerve fibers that act on the feeling of pain.

P. And looking for the pain, they found the temperature …

R. Yes, it was only when we identified the TRPV1 receptor that we understood that it was sensitive to heat.

There is a study that I think is very interesting, in which people living in northern climates have differences in TRP channels compared to those living in warmer climates.

P. Are TRPV1 and TRPM8 responsible for several people who have greater or lesser sensitivity to cold and heat?

R. Genetics has not yet answered this question, but there is a study that I think is very interesting in which people living in Nordic climates have different differences in TRP channels compared to those living in warmer climates .

P. What are you currently working on?

R. We remain fascinated by these questions. Half of my lab is interested in digging deeper into these molecules and the biophysical infrastructure; and the other half, in understanding the molecular and cellular components of the various types of chronic pain.


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