Abstract
The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tissues (such as the heart, gut, nasal cavity and lungs) and cell types (chemosensory, smooth muscle, endothelial, epithelial and inflammatory cells). Although it is still not clear whether endogenous T2R agonists exist, the T2R receptors recognize many natural and synthetic compounds, such as the acyl-homoserine lactones produced by bacteria, caffeine, chloroquine, and erythromycin. In the upper airways, T2Rs are involved in neurogenic inflammation and bacterial clearance. Their known effects in the lungs are exerted at three different levels. Firstly, T2R agonists increase the beating frequency of cilia on epithelial cells. Secondly, the T2Rs induce bronchial smooth muscle cells to relax. Thirdly, the T2R receptors expressed on immune cells (such as macrophages and mast cells) modulate production of pro-inflammatory mediators. Furthermore, T2R agonists are effective in inhibiting lung inflammation or smooth muscle contraction in ex vivo and asthma animal models, and are known to be involved in bacterial killing in the nasal cavity and enhancing lung function in humans. This review focuses on the pharmacology and physiological functions of T2R receptors in the upper and lower airways. It presents recently acquired knowledge suggesting that T2Rs may become valuable drug targets in the treatment of diseases such as asthma and chronic rhinosinusitis.
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