The same bitter taste receptors that are found on the human tongue also exist in the smooth muscles of the lungs, according to research published online yesterday in Nature Medicine. The unexpected findings could lead to improved treatments for asthma, emphysema and chronic bronchitis.
Stephen Liggett and his colleagues at the University of Maryland School of Medicine in Baltimore stumbled upon the taste receptors when looking for G protein-coupled receptor proteins in airway smooth muscle cells. The discovery intrigued them because taste receptors, when activated, typically increase the amount of calcium within the cell, causing muscle constriction. So Liggett’s team assumed that this chemical flux would constrict the lung tissue.
But when they stimulated the receptors in a mouse model of asthma with compounds known to activate bitter taste buds, including quinine and saccharine, the researchers were surprised to find that the muscles relaxed, presumably because the receptors in the lungs evolved to help people breathe more easily in the presence of bitter foreign substances, such as those secreted by pathogenic bacteria during bronchitis or pneumonia.
Liggett’s team is now actively screening compounds to find the ones that most effectively and safely open lung airways.
“There have not been any new direct bronchodilators in the drug discovery pipeline in over five decades,” Liggett told Nature Medicine. “And we have now found a pathway and multiple drugs that activate that pathway that provide direct bronchodilitation that’s more extensive than any known pathway or compound to date.”
The work will appear in the November issue of the journal, and an extended interview with Liggett can be heard on next month’s podcast.