Could a bitter compound provide clues about how to treat asthma?

For a long time, scientists thought the taste receptors that signal sweet, bitter, or salty were found only in our taste buds. Then, things started to get weird.

Six years ago, researchers found taste receptors in the cells of the gut. Even more bizarre, scientists found them in cells that line the airway, and in the muscles that contract during an asthma attack. Basic scientific research began to suggest that bitter chemicals had potential as a new class of asthma treatment. That’s when Ronghua ZhuGe, at the University of Massachusetts Medical School, began to pay attention.

ZhuGe is a microbiologist who studies cell signaling involved in muscle function, a process that helps regulate blood pressure or airway constriction. He was intrigued and puzzled when he read about experiments that demonstrated bitter compounds could cause those muscle cells to relax, pointing to a potentially powerful way to quell an asthma attack.

In that initial paper, the researchers called it a paradoxical result. Based on existing knowledge and scientific intuition, they expected the bitter compounds would have the opposite effect, causing airway cells to contract. That would add to the problems patients experience in diseases caused by airway obstruction, such as asthma and chronic obstructive pulmonary disorder. But instead, bitter substances caused the cells to relax. ZhuGe decided to study how the nose-wrinkling compounds had that effect.

In a study published Tuesday in the journal PLOS Biology, ZhuGe and colleagues tease out the precise cellular mechanisms at work when bitter stuff, such as quinine and denatonium—ZhuGe calls it the most bitter compound that exists—are administered to those airway cells. The scientists took freshly procured muscle airway cells from mice and carefully figured out the complicated signaling that results in the relaxation of the cells. That’s the goal with asthma medications, called bronchodilators.

“Definitely, we see a great potential to develop a new class of bronchodilators,” ZhuGe said. “When we compare how effective those compounds are to relax airways, we found we can relax them more completely compared” to existing treatments.

ZhuGe said the prospects are particularly exciting because there are so many bitter compounds in chemical libraries that could now be tried out as potential new asthma treatments. The search will be guided, he hopes, by a more precise understanding of the mechanism at play when airway cells relax in response to a bitter stimulant.

But that won’t answer the question most people have: why did bitter taste receptors ended up in our lungs in the first place? ZhuGe said his guess is basically as good as anyone else’s—“pure speculation.” It could be a protective mechanism; perhaps its advantageous to have cells relax instead of contract when inhaling a bitter compound.