With the recent discovery of bitter taste receptors in the lungs, a lot of questions have been raised about the implications such a discovery might have on the future treatment of asthma and other respiratory illnesses. Below, the study's senior author Dr. Stephen Liggett, professor of medicine and physiology at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program, answers some frequently asked questions about this groundbreaking research.
In individuals with asthma, the smooth muscle surrounding the airways contract or tighten, which impedes the flow of air and causes wheezing and shortness of breath. According to the American Lung Association, asthma affects nearly 23 million Americans, including seven million children.
When we used various tools to examine expression of receptors on the cell surface of the bronchial smooth muscle of the lung, which is the part that constricts the airways in asthma and COPD patients, we found multiple members of the family of bitter taste receptors; receptors that we knew were on cells on the tongue but not on airway smooth muscle.
The detection of functioning taste receptors on the smooth muscle of the lungs was actually so unexpected that we were first quite skeptical ourselves. Our lab has an ongoing effort to find lung muscle receptors that regulate airway contraction and relaxation, and while the data showing taste receptors was in our computer, we didn't make the connection that they might be functional.
On the tongue, we know that these specialized receptors appear to evoke an aversion response to bitter tastes, many of which are toxic. Consequently, it seemed logical to us that the purpose of the lung's taste receptors would be much the same -- to signal the presence of an inhaled toxin. Initially, we thought the bitter taste receptors in the lungs would prompt a "fight or flight" response to a noxious inhalant, causing chest tightness and coughing, prompting an individual to leave the surrounding toxic environment. We also considered that these receptors may be the basis for occupational asthma, where chemicals in the air in the workplace cause asthma symptoms. However, that's not what we found.
It turns out that the bitter compounds worked the opposite way from what we thought. These compounds actually opened the airway more extensively than any known medication we have for treatment of asthma or COPD.
We picked some standard bitter compounds that are known to activate these receptors and tested them under various circumstances. This included watching individual cells under the microscope, and the action of these compounds on intact airways. Upon coming into contact with the tissue, these compounds actually relaxed the muscle so extensively that we were worried that the effect was due to damaging the muscle. But this was not the case.
There have not been any new direct bronchodilator medications available for asthma or COPD in decades. Currently, the only direct bronchodilators we have are the beta-agonists, which include drugs like albuterol that are usually taken using an inhaler. But, at least half of all asthma patients have inadequate control of the disease using current medications, so there is a recognized need for new treatments. Our findings, once further developed, could lead to a completely novel class of bronchodilators which could enhance current drugs or become part of a new approach to the treatment of asthma and other respiratory illnesses.
How these agents would fit into the current ways we treat asthma is speculative at this point, since we have not tested them in people. If they are as effective as the studies show in the lab, and they have a good safety profile, they could replace beta-agonists, or, become part of an add-in scheme for those patients who are not controlled by traditional therapy.
We want to caution people that eating bitter tasting foods or compounds will not help in the treatment of asthma. Based on our research, we think that the best medications would be chemical modifications of bitter compounds, which would be aerosolized and then inhaled into the lungs with an inhaler.
Now that we have made this discovery, we want to proceed with clinical trials. First, we will have to find which compounds that act at these receptors on bronchial smooth muscle evoke the best relaxation response. After we have our compounds, we will then have to successfully complete a variety of human and non-human trials in different phases to test the efficacy, tolerability and toxicology of these compounds. This is often a tedious task. Fortunately, there are over 10,000 known bitter substances that are found in nature or have been synthesized for other purposes. So, we have a lot of possible agents to work with.
The twists and turns of this discovery have reaffirmed my personal attraction to science. We should always be looking for that glimmer of light in the "corner" of an experiment that might tell us something really new, that can make a difference in understanding or treating a disease.
This page was last updated on: October 22, 2010.