Saturday , December 4 2021

Nobel Prize in Medicine: “We must investigate the components of the inflamed soup”



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

Julius, a professor and chair of the Department of Physiology at the University of California, San Francisco (UCSF), was announced as the winner last week, along with his Scripps Research colleague Ardem Patapoutian, for their discovery of receptors for temperature and touch.

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

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

Question. Why are TRP channels important? What would happen to us humans if we didn’t have these receptors?

Reply. That’s hard to say. It is a very large family of molecules that perform functions for cells ranging from absorbing calcium to sensing pain. There are people who have mutations in TRPV4 that are important for bone development and therefore have skeletal or nervous system defects. What I can say is that if someone had missed all the TRP channels, that person would have been dead.

p. What if only TRPV1 and TRPM8 (the two described by Julius that sense heat and cold) are missing?

r. So what I can say is that when we remove these receptors from lab mice, they don’t die. They have deficits, but they live, albeit in a very controlled environment. These receptors play a role in detecting changes in temperature, so you will have a hard time knowing what the ambient temperature is and not your body temperature.

p. Is this something tried?

R. Yes. When a person is given drugs that block TRP channels, they have trouble detecting anything hot. This worries pharmaceutical companies, for example, who don’t want someone to burn them because they no longer sense a very hot cup of coffee as sensory.

p. Can we live without pain?

r. There are people who have mutations in other types of molecules that cause them to be unable to perceive any pain stimuli. You have to be very careful and watch over them when they’re young, but if they get past this stage and learn what to watch out for even if they don’t feel pain, they can live a pretty good life. When the molecules we studied are removed, only some components of the pain disappear, so it’s not a dramatic deficiency.

When the molecules we studied are removed, only some components of the pain disappear, so it’s not a dramatic deficiency.

p. And are these molecules present in all animals?

R. In general, yes.

p. How will the molecules sense the temperature (TRPV1 and TRPM8)?

R. We always describe them as a donut in the cell membrane. For example, they are at the end of a sensory nerve in the skin or tongue and are shaped like a small doughnut. Under normal temperature conditions, the ring hole is closed, but when they come into contact with something hot or cold, the TRP channel is activated and the hole expands.

p. Then what goes through that hole?

R. Calcium and sodium ions enter the cell through the hole, generating electrical currents to the neurons, and that’s when they react and say, “I’m on fire!” we say. or “How cold is that!”

p. And what good does that do 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 say we go to the beach and burn our skin. Later, the back becomes inflamed and very sensitive to temperature changes, so when we shower with hot water it gives us the feeling of burning. This tells us that this part of the body is injured and we must protect it until it heals.

This tells us that part of the body is injured and we must protect it until it heals.

p. In addition to heat, TRPV1 also reacts when it comes into contact with acid. Why?

r. Heartburn, like heat, is another component of what we call “inflammatory soup.” It is an agent that contributes to inflammation to increase the sensitivity of that part of the body when an injury occurs. It is very important to study all the ingredients in this “soup” in order to create medicines that are effective in reducing pain without interfering with basic functions such as heat perception, thereby preventing people from burning unnoticed.

p. You started your research with capsaicin, the chemical compound found in cayenne peppers like cayenne pepper. Why exactly did you choose this compound?

r. We chose capsaicin because we wanted to study pain in general. Pepper is a spice that has long been used as a medicine, and we knew that capsaicin is a very powerful activator of nerve fibers that affect the sensation of pain.

p. And in search of pain they found warmth …

r. Yes, we didn’t realize it was heat sensitive until we identified the TRPV1 receptor.

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

p. Are TRPV1 and TRPM8 responsible for different people with greater or lesser sensitivity to cold and heat?

R. Genetics has yet to answer this question, but there is a study that I think is very interesting given that people living in Scandinavian climates have differences in TRP channels compared to those living in warmer climates.

p. What are you currently working on?

R. We continue to be 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 different types of chronic pain.

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