First, a screen of isolated human ASM looking for new G protein-coupled receptor (GPCR) targets, which are the major receptor family controlling ASM relaxation and constriction, unexpectedly identified bitter taste receptors (the taste receptor type 2 (TAS2R) family) in this tissue. Based on the activity of such receptors on the tongue, which signal in a similar manner to that of known bronchoconstrictive GPCRs, the authors initially postulated that they might protect against inhaling toxic agents by causing constriction of the airways. However, the opposite effect was seen following activation of these bitter taste receptors in ASM.
TAS2R10, TAS2R14 and TAS2R31 were found to be the most highly expressed TAS2R subtypes in ASM. Evaluation of bitter tastants such as saccharin, chloroquine and denatonium in isolated ASM evoked a calcium response. However, stimulation of human ASM, mouse airways and bronchi obtained from non-diseased portions of human lung tissue resulted in relaxation in a dose-dependent manner. Moreover, the relaxation response was threefold greater than that of relaxation brought about by the β-adrenergic receptor agonist isoproterenol. In addition, chloroquine and isoproterenol induced greater relaxation of airways than either compound alone, indicating that bitter tastants have additive effects with β-adrenergic receptor agonists. In a mouse model of acute airway inflammation, aerosolized quinine reversed bronchoconstriction to a higher degree than inhaled albuterol — a β-adrenergic receptor agonist that is commonly used to treat asthma.
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