D.A. Deshpande et al., “Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction,” Nat Med, 16:1299-304, 2010. Free F1000 Evaluation

The finding

Stephen Liggett and colleagues at the University of Maryland School of Medicine set out to identify the G-protein coupled receptors (GPCRs) involved in the contraction of bronchial airway muscles that can lead to asthma. They discovered bitter taste receptors—previously only found on the tongue—on airway smooth muscle (ASM) cells, and showed that their activation causes bronchial relaxation instead.

The surprise

Liggett thought these receptors might protect against inhaled toxic substances. When his lab treated ASM cells with bitter-tasting compounds, such as saccharin or chloroquine, they saw an increase in intracellular calcium concentration—a hallmark of smooth muscle contraction, and thus presumably of bronchoconstriction. “We were thinking we’d found the cause of occupational asthma,” Liggett says. Surprisingly,...

The relaxation

The bitter-tasting molecules very rapidly activated highly localized stores of calcium, rather than the slower, cell-wide calcium release that causes constriction. The team repeated the test in live mice, and saw the same result. “It was like nothing we had ever seen before,” Liggett says.

The drugs

There are “10,000 or more” known activators of bitter taste receptors, some of which are already used in medicine. The only issue would be making them more palatable, but that doesn’t bother Liggett much. “We’ve got more compounds than we can study,” he says.

F1000 evaluators: J. Martin (McGill Univ) E. Schneider & P. Murphy (NIAID) B. Nilius (KU Leuven)A. Morris & D. Spina (King’s Col London)

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