Breathe better with bitter

Lungs relax when hit with acrid gases

Inhaling a blast of bitter fumes sends a breathe-easy message to the lungs, a new study shows. Stimulating bitterness receptors in the lungs relaxes and opens the airways, a counterintuitive finding that could lead to new asthma medications, scientists report online October 24 in Nature Medicine.

Bitter-taste receptors just like the ones on the tongue abound on the smooth muscle tissue that wraps around the airway tubes leading to the lungs, reports a team from the University of Maryland and Johns Hopkins in Baltimore. In mice bred to have asthma, inhaled bitter compounds such as quinine did a better job of relaxing airways than did the standard asthma drug albuterol.

These bitter-taste receptors in lung muscles should be good targets for new asthma medications that are based on the multitude of molecules known to stimulate bitter receptors, says Mathur Kannan, a pharmacologist in the College of Veterinary Medicine at the University of Minnesota in St. Paul. 

The relaxation response to bitter-flavored air remains somewhat puzzling. In the mouth, bitter receptors are part of the body’s first line of defense against possibly poisonous compounds. Cells lining the upper part of the respiratory tract also have bitter-taste receptors, scientists reported last year. But there, they can trigger an “out, out” reaction, stimulating the featherlike cilia of the airways to push whatever’s nearby up and away. So it seemed more logical that muscles controlling air flow to lungs would constrict when stimulated by potential toxins, says Stephen Liggett of the University of the Maryland School of Medicine in Baltimore, who led the new work.

“We thought it might be a cause of occupational asthma, an aversion response,” he says. For human ancestors faced with an environment laced with bitter fumes, shutting down airways would make breathing difficult, forcing departure from an unhealthy place. “It would make you run out of a cave if you were in a noxious environment,” says Liggett.

But it turns out that triggering these bitter receptors triggers a “relax, chill out” response, several experiments have demonstrated with cells and lung tissue from mice and humans. Opening the airways may aid in clearing infection, the scientists speculate. Previous research revealed that some signaling molecules made by bacteria also activate bitter receptors. Perhaps relaxed airways prevent lung infections from festering.

“When you get a lot of gunk in there it leads to a closed airway,” Liggett says. “That would have been fatal in the days before antibiotics.”

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