Taste 2 receptors

PHILADELPHIA, July 29, 2024 /PRNewswire/ -- The tastebuds of the tongue contain bundles of specialized cells bearing sensors that detect chemical attributes of food. Known as taste receptors, these sensors were long believed to reside only on the tongue. Marco Tizzano, an associate professor in the Department of Basic & Translational Sciences at Penn Dental Medicine, was among those who discovered them in many places elsewhere in and on the body. He has since documented taste receptors throughout the airways, especially in the nose, but also the trachea and the lungs, as well as the gums and even dental pulp. These sensors, he and others have found, detect bacterial pathogens and allergens, then alert the innate immune system. Tizzano's research has shown that bitter sensing taste receptors in the nose respond to a compound bacteria use to communicate. These sensors then activate the trigeminal nerve, a cranial nerve that provides sensation to the face, leading to a significant inflammatory response. Bitter taste receptors also show up in the gums. In experiments, Tizzano's research team demonstrated that in gum tissue these receptors actually offer some natural protection against periodontitis, the most severe form of gum disease. After sensing pathogenic bacteria, they trigger the production of antimicrobial peptides to kill the germs. Without these receptors, mice suffered from more damaging periodontitis, the researchers found. In another line of study, Tizzano's lab is looking at odor-detecting receptors found on neurons in dental pulp. When these relatives of the taste sensors detect eugenol, an odor molecule from cloves, they numb the teeth. As someone who looks for connections between disciplines, Tizzano ultimately seeks to use naturally occurring compounds, such as eugenol, to stimulate these receptors in ways that benefit health. Such applications could include a new form of pain relief for dental procedures or a therapy to stifle the microbial growth triggering the inflammation that drives periodontal disease. "I think we are still at the tip of the iceberg," Tizzano says. "There is so much more to discover about these receptors." Media Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE

Strong bitterness is the main reason why people all over the world, especially children, avoid taking their medicines, putting their health, and sometimes, their lives at risk. Now, a group of scientists has identified the first temporary, universal taste blocker that works in people. Many people, especially children and the elderly, have difficulty swallowing pills. Liquid forms of many medicines taste extremely bitter and are often rejected. Put simply, strong bitterness is the main reason why people all over the world, especially children, avoid taking their medicines, putting their health, and sometimes, their lives at risk. Now, a group of scientists at the Monell Chemical Senses Center identified the first temporary, universal taste blocker that works in people. Their findings appear in the British Journal of Pharmacology. "Remarkably, and unlike our experience with blockers of bitter taste receptors, the taste-nerve blocker we tested worked for every subject and every bitter compound we tested," said first author Linda J. Flammer, PhD, Monell Senior Research Associate and Director of the Corporate Partners Program. "I have never seen this before." Until now, efforts to block bitterness in foods and medicines have focused on finding blockers for bitter taste receptors on the tongue. Because different medications activate distinct sets of bitter taste receptors, targeting specific receptors may only suppress bitterness for certain, but not all, bitter-tasting compounds. "There is a clear need to develop bitter blockers that are able to suppress the bitterness of many medications," said co-author Carol Christensen, PhD, Monell Alumnus Faculty Member. "Although humans have 25 different bitter receptors, our ongoing research suggests only a handful of bitter receptors may be responsible for most of the bitterness of medicines." Taste cells in the mouth that express the TAS2R family of taste receptors are stimulated by sweet, bitter, and savory compounds, and transmit signals to nerve fibers by releasing adenosine triphosphate (ATP), a cell's main source of energy. In turn, ATP activates a receptor called P2X2/P2X3 on the receiving nerve cells. These nerves send information to the brain about the taste of foods and medications. The team used an inhibitor of P2X2/P2X3 receptors, called AF-353, to block taste-nerve transmission and reduce the bitterness signal caused by medications and other taste compounds. Several blockers of P2X2/P2X3 receptors have been identified, with some tested in clinical trials to treat chronic cough; however, a side effect in these trials was taste disturbance. The Monell team capitalized on the "side effect" of these compounds to create an oral treatment that enhances the palatability of medicines. A key finding of the study is that rinsing the mouth with AF-353 significantly reduced the bitterness of two important medicines that treat common chronic diseases: Praziquantel for parasites and Tenofovir Alafenamide (TAF) for hepatitis B and HIV. "AF-353 is the first universal bitter taste blocker that has been identified," said Monell Faculty Member Peihua Jiang, PhD. "In addition to bitter taste, it also affects savory, salt, sweet, and sour tastes. However, AF-353 only blocks taste. Other oral sensations like the tingle from carbonation were not affected." The team conducted both human sensory taste testing and mouse behavioral experiments to determine the breadth, strength, and duration of the blocking effects. The results of the human and rodent studies were similar in the breadth and duration of AF-353's action. The topical application of AF-353 directly into the mouth may improve compliance of many important medications, especially those that are life-saving for children in developing countries. "In people, the blocking effect lasted 60 to 90 minutes, when their taste was restored to normal," said Flammer. "We are now looking for taste blockers that act faster and allow taste to return to normal sooner," said Jiang.orted by the Bill & Melinda Gates Foundation (INV-037008 and INV-042630). The behavioral work was performed at the Monell Behavioral and Physiological Phenotyping Core, which is supported, in part, by the National Institutes of Health (NIH) NIDCD Core Grant 1P30DC011735-01. Research infrastructure was provided in part by NIH Grant G20OD020296.

In the stomach, so-called parietal cells are responsible for acid production. They react not only to the body's own messenger molecules, but also to bitter-tasting food constituents such as caffeine. A research team has now carried out a study on a human gastric cell line. Their results help to clarify the molecular regulatory mechanisms by which bitter substances influence gastric acid production. In the stomach, so-called parietal cells are responsible for acid production. They react not only to the body's own messenger molecules, but also to bitter-tasting food constituents such as caffeine. A research team from the Leibniz Institute for Food Systems Biology at the Technical University of Munich has now carried out a study on a human gastric cell line. Their results help to clarify the molecular regulatory mechanisms by which bitter substances influence gastric acid production. It is known that taste receptors for bitter substances are not only found on the tongue, but also on the surface of other tissues and cells. These include the parietal cells of the stomach, which secrete protons into the stomach -- i.e. produce gastric acid. Recent studies have already shown that the bitter taste receptors found in parietal cells are involved in the regulation of gastric acid release. However, the underlying molecular signaling pathways are not yet fully understood. Gastric cells as a test system To further clarify the molecular interaction between bitter substances, bitter taste receptors, and gastric acid production, a research team led by Veronika Somoza, Director of the Leibniz Institute in Freising, has carried out a study on a cellular test system. This involves human parietal HGT-1 cells, which are able to secrete protons and, like taste cells, have bitter taste receptors. Veronika Somoza's team initially developed a working hypothesis based on the results of previous studies and the findings on signal transduction pathways in taste cells. According to this hypothesis, bitter tasting food constituents stimulate bitter taste receptors that are embedded in the cell membrane. This releases calcium ions inside the cells, leading to ion channel opening. This, in turn, allows sodium ions to flow into the gastric cells from the outside, ultimately contributing to the release of protons. Hypothesis confirmed First author Phil Richter explains: "We have successfully tested this mechanism with the two bitter substances caffeine and l-arginine. As expected from previous results, both food constituents were shown to stimulate gastric cell proton secretion in our test system." The PhD student adds: "For the first time, we were able to demonstrate that the transient receptor potential channelsM4 and M5 are involved in the signaling cascade not only in taste cells but also in gastric cells and ensure an influx of sodium ions into the cells." Senior Scientist Gaby Andersen says: "By using knock-out experiments, in which we specifically switched off one type of bitter taste receptor in the cells, we were also able to show for the first time that there is a link between bitter taste receptors and the activation of the ion channels." The scientist emphasizes that the results not only contribute to a better understanding of the role of taste receptors in the stomach but would also show that HGT-1 cells could be suitable as a replacement model for taste cells. The research team agrees that the results will provide new insights into the regulation of gastric acid production and thus lead to innovative approaches in treating gastric diseases in the long term. However, further studies are needed to deepen knowledge of the molecular regulatory mechanisms and intracellular signaling pathways.