Role of TAS2R38 polymorphism in respiratory diseases pathogenesis

Abstract

More and more new data, concerning extraoral bitter taste receptors (TAS2R), appear now. Current data on polymorphisms, expression patterns and form of TAS2R subtype 38 (TAS2R38), its molecular variants that differ in the degrees of sensitivity to ligands and their role in the pathogenesis of respiratory disorders are discussed in this review. The mechanism of signal transduction from taste receptors mediated by G-protein is shown. Participation of TAS2R38 in the local protective mechanisms in a ciliated epithelium of the respiratory tract and its activation by “quorum sensing” system molecules and its connection with the components of mucociliary clearance are presented. It has been shown that the action of the ligand on the TAS2R38 leads to the activation of NO synthase, followed by the production of nitric oxide (NO), which triggers a number of intracellular reactions leading to an increase in the rate of beating of the cilia of the ciliary epithelium, as well as having a direct antibacterial effect. TAS2R38 are also found on leukocytes, and its expression decreases with age, which can be considered as a component of the general aging of immunocompetent cells in the body. It is known that activation of TAS2R38 also enhances the phagocytic activity of macrophages, which is also mediated by the action of G-protein and cGMP. TAS2R receptors are also considered to be associated with allergic diseases, in particular – with bronchial asthma. A number of studies in groups of children with bronchial asthma revealed that the expression of most TAS2Rs was higher in children with severe bronchial asthma. Other studies have shown that patients with the eosinophilic variant of chronic rhinosinusitis have a higher levels of TAS2R38 expression in the upper respiratory tract compared to those with chronic rhinosinusitis without eosinophilia. To date, the functional significance of extraoral bitter taste receptors has not been fully studied. In the future, a large amount of research work remains to be done to finally understand the role of TAS2R in the pathogenesis of respiratory diseases.