Oct. 4 - RIA Novosti
What the feeling of bitterness and hotness have in common
The human ability to feel pain has long been a mystery to science. A Hungarian scientist, Miklos Jancsó, came close to solving it in the late 1940s. Together with his colleagues, he experimented with capsaicin, a substance found in chili peppers.
Jancsó smeared the pepper on his face and hands, applied it to test animals in the laboratory and monitored their behavior. And he found that when the skin was exposed to it for a long time, the burning stopped. Other bitter stimuli, such as mustard, also caused a reaction. He also noted: if you put capsaicin on half of your face, in addition to the burning pain, you can feel that the skin becomes hotter.
Jancho's work showed how the peripheral nervous system reacts to pain and gives signals to the brain. However, it was still unclear exactly how pepper triggers the process of nerve impulse birth. There had to be some kind of "capsaicin" receptor. It was discovered in 1997 by David Julius of the University of California, San Francisco, grandson of immigrants from Russia.
Born into an intelligent family in New York, Julius graduated from the Massachusetts Institute of Technology and chose neurobiology. He was interested in how our cells respond to external stimuli: chemical molecules, mechanical and physiological stimuli. Julius and his colleagues cloned DNA fragments, making them work in cells that were definitely unresponsive to capsaicin. So they discovered the right gene and named it the type 1 vanilloid receptor, TRPV1.
TRPV1 is a protein that is produced in the membrane of nerve cells that permeate the skin, mucosa, many internal organs, and the brain. It works as an ion channel: when activated, it begins to allow sodium, magnesium, and calcium ions into the cell. As a result, an electric potential accumulates, triggering a chain of nerve impulses, and we feel pain. As it turns out, the receptor is triggered not only by capsaicin, but mainly by heat. We feel pain if our skin temperature rises to 43 degrees or higher.
There is a whole group of TRP receptors that are involved in the formation of acute and chronic pain. One of them, TRPV8, activates when the temperature is below 16 degrees and it also reacts to mint: it gives the sensation of cold. Julius also discovered a special receptor for wasabi, a spicy substance contained in mustard extract.
Discovery of the stroking receptor
Ardem Pataputyan was born in Beirut to an immigrant family of Armenian descent. As a student, he came to the United States and studied at the University of California, Los Angeles. After his doctorate, he worked in San Francisco, where he intersected with Julius. At that time, independently of each other, they discovered the cold receptor TRPV8.
At the Howard Hughes Medical Institute and the Scripps Institute, Pataputyan and his colleagues began investigating touch, the only one of the senses whose molecular mechanism of operation remained unknown. Scientists speculated that it begins in the skin with a physical stimulus, then transforms into a chemical stimulus and then into a nerve impulse. This is all very similar to the sensation of temperature and pain.
Scientists experimented with a culture of cells, piercing them with a micropipette. And they identified which ones responded with an electrical nerve impulse. Next, they selected 72 candidate genes. Using RNA interference, they were able to calculate the desired coding receptor and isolate it. The protein was given the telling name "piezo." This is how two receptors of this group were discovered - Piezo 1 and Piezo 2.
Piezo 2 sends signals to the brain that our bladder is full, that someone is touching our skin lightly, or that we are sunburned. These sensors also sense the relative position of our body parts. Pataputian's work started a whole field, mechanobiology.
Julius and Pataputyan have jointly won a number of major awards in the field of physiology: the BBVA Medical Breakthrough Award, the Kavli Prize, the Heardner International Prize. Now the Nobel Committee, too, has praised the fundamental nature of their achievements.
"They understood how the body functions. When they awarded the prize, they specified that they actually gave it for the description of the somatosensory mechanism - the way the body perceives the world around it - this is temperature and exposure," explains Valentin Borschevsky, deputy head of the MIPT Laboratory of Advanced Membrane Protein Research.
According to the scientist, the systems that perceive touch and temperature are very simple. Only one protein is responsible for each of these sensations. "This is a pretty rare situation," he noted.
The discoveries have yet to find practical applications. "How this knowledge can be used in medicine, we will know in the near future. I think first of all, to create drugs against pain. Or tools to influence cells - not only for research, but also for cellular therapies," Borschevsky added.
Julius and Pataputyan's research opens up prospects for the development of neopioid painkillers. Several pharmaceutical laboratories around the world are already looking for a compound that could become the basis for drugs against arthritic pain.