Taste Buds in the Lungs Could Alleviate Asthma

A new study has found that bitter taste receptors on the smooth muscle of the bronchus cause bronchodilation by localized calcium signaling and reverse obstruction.

Researchers at the University of Maryland (UMD, College Park, USA) discovered the existence of unorganized bitter taste receptors (TAS2Rs) on human airway smooth muscle (ASM) in the lungs. The researchers hypothesized that these receptors were similar to those on the tongue, and served as avoidance receptors for inhalants that, when activated, lead to ASM contraction and bronchospasm. To test this theory, they exposed bitter-tasting compounds to human and mouse airways, individual airway smooth muscle cells, and to mice with asthma.

To their surprise, they found that bitter tastants actually caused relaxation of isolated ASM and dilation of airways, an effect that was threefold greater than that elicited by β-adrenergic receptor agonists. The relaxation induced by TAS2Rs was found to be associated with a localized intracellular calcium ([Ca2+]i) response at the cell membrane, which opens large-conductance Ca2+-activated K+ channels, leading to ASM membrane hyper-polarization. In mouse asthma models, inhaled bitter tastants decreased airway obstruction. The study was published early online on October 24, 2010, in Nature Medicine.

"It turns out that the bitter compounds worked the opposite way from what we thought; they all opened the airway more extensively than any known drug that we have for treatment of asthma or chronic obstructive pulmonary disease,” said lead author Stephen Liggett, M.D., a professor of medicine and physiology. "New drugs to treat asthma, emphysema, or chronic bronchitis are needed. This could replace or enhance what is now in use, and represents a completely new approach.”

ASM mass is increased in patients with asthma, and is quite marked in lung sections from patients who have died of asthma. Bronchial-biopsy studies indicate, however, that even persons with mild-to-moderate asthma have increased ASM mass. Both hypertrophy and hyperplasia appear to contribute to this increase, and it is possible that ASM hyperplasia in asthma stems from the inflammatory milieu surrounding the asthmatic muscle.

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