Freund Jenna R, Lee Robert J
Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
World J Otorhinolaryngol Head Neck Surg. 2018 Mar 16;4(1):67-76. doi: 10.1016/j.wjorl.2018.02.004. eCollection 2018 Mar.
Taste receptors were named for their originally-identified expression on the tongue and role in the sensation of taste (gustation). They are now known to be involved in many chemosensory processes outside the tongue. Expression of the receptors for bitter, sweet, and umami was recently identified in many organs, including the brain, airway, gastrointestinal tract, and reproductive systems. We do not yet know the full roles of these receptors in all of these tissues, nor do we know all of the endogenous ligands that activate them. However, taste receptors are emerging as potentially important therapeutic targets. Moreover, they may mediate some off target effects of drugs, as many medications in common clinical use are known to be bitter. The focus of this review is on recent basic and clinical data describing the expression of bitter (T2R) and sweet (T1R) receptors in the airway and their activation by secreted bacterial compounds. These receptors play important roles in innate immune nitric oxide production and antimicrobial peptide secretion, and may be useful targets for stimulating immune responses in the upper respiratory tract via topical therapies. Moreover, genetic variation in these receptors may play a role in the differential susceptibility of patients to certain types of respiratory infections as well as to differential outcomes in patients with chronic rhinosinusitis (CRS). CRS is a syndrome of chronic upper respiratory infection and inflammation and has a significant detrimental impact on patient quality of life. CRS treatment accounts for approximately 20% of adult antibiotic prescriptions and is thus a large driver of the public health crisis of antibiotic resistance. Taste receptors represent a novel class of therapeutic target to potentially stimulate endogenous immune responses and treat CRS patients without conventional antibiotics.
味觉受体因其最初在舌头上被发现的表达以及在味觉（味觉感知）中的作用而得名。现在已知它们参与舌头以外的许多化学感应过程。最近在包括大脑、气道、胃肠道和生殖系统在内的许多器官中发现了苦味、甜味和鲜味受体的表达。我们尚不知道这些受体在所有这些组织中的全部作用，也不知道激活它们的所有内源性配体。然而，味觉受体正逐渐成为潜在的重要治疗靶点。此外，它们可能介导药物的一些脱靶效应，因为许多常用临床药物都是苦的。本综述的重点是描述气道中苦味（T2R）和甜味（T1R）受体的表达以及它们被分泌的细菌化合物激活的最新基础和临床数据。这些受体在先天性免疫一氧化氮产生和抗菌肽分泌中起重要作用，并且可能是通过局部治疗刺激上呼吸道免疫反应的有用靶点。此外，这些受体的基因变异可能在患者对某些类型呼吸道感染的易感性差异以及慢性鼻-鼻窦炎（CRS）患者的不同结局中起作用。CRS是一种慢性上呼吸道感染和炎症综合征，对患者生活质量有重大不利影响。CRS治疗约占成人抗生素处方的20%，因此是抗生素耐药性公共卫生危机的一个主要驱动因素。味觉受体代表了一类新型治疗靶点，有可能刺激内源性免疫反应并在不使用传统抗生素的情况下治疗CRS患者。
