Breathe Bitter, Breathe Easy!

The ability to taste bitter substances might serve a protective function, helping us to avoid bitter-tasting toxins. Bitter taste receptors occur not only in the taste buds of the tongue, however, but also in the nasal passage and motile cilia of the airways. Deshpande et al . now find that these receptors are also expressed by the airway smooth muscle cells, where, surprisingly, they relax the airways. This is a finding with potential medical relevance for asthma and certain other lung diseases, which are characterized by airway constriction. These conditions are often treated with β-adrenergic receptor agonists (β-agonists), which cause dilation of constricted airways, but such treatments are only partially effective. The authors initially found that bitter substances—known to be bitter taste receptor agonists—induced intracellular calcium signaling responses in primary human airway smooth muscle cells; subsequent analysis showed that four bitter taste receptors were expressed on the surface of these cells. These receptors were important for airway relaxation as revealed in experiments involving intact mouse airways, in which the bitter substances relaxed contractions induced by acetylcholine. The relaxation was reversible (indicating that it was not caused by injury to the cells), independent of cyclic adenosine monophosphate (in contrast to relaxation induced by β-agonists), and additive with that caused by β-agonists. Using a mouse asthma model, the authors further demonstrated that certain bitter substances decreased airway resistance to a greater extent than albuterol, a β-agonist bronchodilator commonly used for treating asthma. The effect of bitter substances was additive with that of β-agonists in these mice, suggesting that the two may act independently and could be used together as combined therapeutic strategy. However, the researchers cautioned that the bitter substances are only effective when inhaled in an aerosol. Together, these experiments show that there might be a sweet side to bitter substances. D. A. Deshpande et al. , Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat. Med. 24 October 2010 (10.1038/nm.2237). [[Abstract]][1] [1]: http://www.ncbi.nlm.nih.gov/pubmed/20972434