Lungs Sense Bitterness Using a Little Bit of Tongue

More than a dozen of the taste receptors found on the tongue also have been discovered in human lungs, and manipulating them could help people with asthma, researchers report.

Surprised scientists found the receptors by accident during a study of molecules in human lung muscle that regulate airway contraction and relaxation. The discovery "was so unexpected that we were at first quite skeptical ourselves," said researcher Stephen Liggett, a pulmonologist at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program.

Specifically, the investigators discovered proteins responsible for tasting bitterness. On the tongue, these receptors are clustered in taste buds, which send signals to the brain. In the lung, the receptors are not clustered in buds and do not send signals to the brain, but they do respond to substances that have a bitter taste. All in all, 17 of the 25 known types of bitter-taste receptors were seen in the lung. No other kinds of taste receptors were found there.

"Finding these receptors in a place where they weren't supposed to be was pretty exciting," Liggett said.

Wheezing mice

To find out what these receptors do in the lung, Liggett and his colleagues exposed bitter compounds to human and mouse airways and to mice with asthma. In asthma, these airways contract, impeding the flow of air, causing wheezing and shortness of breath.

Since most plant-based poisons are bitter, the researchers expected the purpose of the lung's taste receptors would be to warn against poisons.

"I initially thought the bitter-taste receptors in the lungs would prompt a 'fight or flight' response to a noxious inhalant, causing chest tightness and coughing so you would leave the toxic environment," Liggett said. "But that's not what we found."

Unexpectedly, when the researchers tested a few standard bitter substances against these receptors, "it turns out that the bitter compounds worked the opposite way from what we thought," Liggett said. "They all opened the airway more profoundly than any known drug that we have for treatment of asthma or chronic obstructive pulmonary disease."

While compounds known as beta-agonists that are normally used in inhalers for asthma and chronic obstructive pulmonary disease "work fairly well, bitter compounds worked three to four times better in terms of extent of relaxation they could provide," Liggett told LiveScience. "At first it looked like some kind of mistake on our end — that maybe the muscle we tested was damaged and was relaxing as it was dying — but that wasn't the case."

As to why bitter compounds had the opposite effect of what researchers expected, "it turns out bacteria make a bitter substance as they infect the lungs," Liggett said. "Thus, during bronchitis or pneumonia, the body can respond by opening the airways, helping the individual to breathe and to clear the cellular debris, mucus and bacteria from the infection."

Bitter treatment

Asthma and chronic obstructive pulmonary disease together affect 300 million people worldwide, and these numbers are growing. According to the American Lung Association, asthma affects nearly 23 million people in the United States, including 7 million children, and chronic obstructive pulmonary disease is the fourth-leading cause of death in the nation. [Related: Burger and Fries Worsen Asthma]

There are thousands of bitter compounds that, in appropriate doses, are not toxic, and someday the new knowledge may be able to help people with lung problems breathe easier, Liggett said. Quinine and chloroquine, which are very bitter and have been used to treat completely different diseases such as malaria, opened contracted airways profoundly in laboratory models. Even saccharin, which has a bitter aftertaste, was effective at activating these receptors.

"New drugs to treat asthma, emphysema or chronic bronchitis are needed," Liggett explained. "This could replace or enhance what is now in use, and represents a completely new approach."

At least half of all asthma patients do not have adequate control of the disease through the drugs that are currently available.

"Given so many known bitter compounds — at least 10,000 — we have a great opportunity to quickly find a new drug for treating asthma and chronic obstructive lung disease," Liggett said. “We are now screening a large number of bitter compounds to find the ones that are most potent in dilating the airways. From these, we will build compounds that are modifications of these and continue testing. Once we settle on a few compounds, we will formulate them for delivery by aerosol from an inhaler and begin clinical trials.”

Liggett cautioned that eating bitter foods or compounds would not help in treating asthma. "Based on our research, we think that the best drugs would be chemical modifications of bitter compounds, which would be aerosolized and then inhaled into the lungs with an inhaler," he said.

The researchers found aerosol forms of bitter substances could relax the airways of mice with asthma.

The scientists detailed their findings online yesterday (Oct. 24) in the journal Nature Medicine.

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