Taste and smell receptor expression has been traditionally limited to the tongue and nose. We have identified bitter taste receptors (TAS2Rs) and olfactory receptors (ORs) on human airway smooth muscle (HASM) cells. TAS2Rs signal to PLCβ evoking an increase in [Ca^2 +]_i causing membrane hyperpolarization and marked HASM relaxation ascertained by single cell, ex vivo, and in vivo methods. The presence of TAS2Rs in the lung was unexpected, as was the bronchodilatory function which has been shown to be due to signaling within specific microdomains of the cell. Unlike β₂-adrenergic receptor-mediated bronchodilation, TAS2R function is not impaired in asthma and shows little tachyphylaxis. HASM ORs do not bronchodilate, but rather modulate cytoskeletal remodeling and hyperplasia, two cardinal features of asthma. We have shown that short chain fatty acids, byproducts of fermentation of polysaccharides by the gut microbiome, activate HASM ORs. This establishes a non-immune gut-lung mechanism that ties observations on gut microbial communities to asthma phenotypes. Subsequent studies by multiple investigators have revealed expression and specialized functions of TAS2Rs and ORs in multiple cell-types and organs throughout the body. Collectively, the data point towards a previously unrecognized chemosensory system which recognizes endogenous and exogenous agonists. These receptors and their ligands play roles in normal homeostatic functions, predisposition or adaptation to disease, and represent drug targets for novel therapeutics.

传统上，味觉和嗅觉受体的表达仅限于舌头和鼻子。我们已经确定了人气道平滑肌（HASM）细胞上的苦味受体（TAS2Rs）和嗅觉受体（ORs）。TAS2Rs向PLCβ发出信号，引起[Ca ^{2 +} ] _i的增加，引起膜超极化，并通过单细胞，离体和体内方法确定了明显的HASM松弛。TAS2Rs在肺中的存在是出乎意料的，支气管扩张功能也已被证明是由于细胞特定微域内的信号传导所致。不同于β ₂-肾上腺素能受体介导的支气管扩张，TAS2R功能在哮喘中不受影响，几乎没有速激肽。HASM ORs不支气管扩张，而是调节细胞骨架重塑和增生，这是哮喘的两个主要特征。我们已经表明，短链脂肪酸是肠道微生物组多糖发酵的副产物，可以激活HASM OR。这建立了一种非免疫的肠肺机制，将肠微生物群落的观察结果与哮喘表型联系起来。多个研究人员的后续研究表明，TAS2R和OR在整个人体的多种细胞类型和器官中都有表达和特殊功能。总体而言，数据指向先前无法识别的化学感应系统，该系统识别内源性和外源性激动剂。