Increased expression of bitter taste receptors in human allergic nasal mucosa and their contribution to the shrinkage of human nasal mucosa

Objective: Bitter taste receptors (TAS2Rs) are expressed in the extraoral tissues, where they possess various physiological functions. This study is to characterize TAS2Rs expression in normal and allergic nasal mucosa and analyse nasal symptom after challenge with bitter tastes to evaluate their pathophysiological function in normal and allergic nasal mucosa. Methods: The expression levels of TAS2Rs (TAS2R4, 5, 7, 10, 14, 39, and 43) in nasal mucosa were investigated by real-time PCR, Western blot, and immunohistochemistry. The expression levels of TAS2Rs and Ca²⁺ imaging in cultured epithelial cells were measured after stimulation with type 2 cytokines (IL-4, IL-5, and IL-13) or bitter tastes. Nasal symptoms in control subjects and allergic rhinitis patients using visual analogue score and acoustic rhinometry were evaluated before and after stimulation with bitter tastes. Vascular diameter of rat nasal septum was measured before and after treatment with bitter tastes. Results: TAS2Rs tested here were expressed in nasal mucosa where they were commonly distributed in superficial epithelium, submucosal glands, and endothelium. Their expression levels are increased in allergic nasal mucosa and up-regulated in cultured epithelial cells simulated with type 2 cytokines. After treatment with bitter tastes, intracellular Ca²⁺ signalling was increased in cultured epithelial cells, and vascular constriction was found in rat nasal septum. Increased nasal patency was observed in human nasal mucosa without pain or sneezing. Conclusion and Clinical Relevance: TAS2Rs are constitutively expressed in human nasal mucosa and their expression levels are increased in allergic nasal mucosa, where they could potentially contribute to shrinkage of normal and allergic nasal mucosa.