Pathog. BMC Pulm. © 2016 Elsevier Ltd. All rights reserved. Natl. Genomics Hum. Innate Immun. Genet. This discrepancy could stem from difference in the experimental model used in different studies. Nature 527, 512–515. (1998). Life Sci. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Gustducin-expressing epithelial cells are not limited to humans and have been reported to be scattered throughout the nasal epithelium in other species including rodents (Finger et al., 2003). doi: 10.1113/expphysiol.2008.042432, Maurer, S., Wabnitz, G. H., Kahle, N. A., Stegmaier, S., Prior, B., Giese, T., et al.

Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells. doi: 10.1016/j.pharmthera.2011.02.001, Grassin-Delyle, S., Abrial, C., Fayad-Kobeissi, S., Brollo, M., Faisy, C., Alvarez, J. C., et al. 4:2. Collectively, these studies underline the multimodal and pleiotropic manner in which TAS2Rs can be targeted for asthma relief and underline the value of developing TAS2Rs as novel targets for asthma treatment either alone or as an accessory to current regimens (Figure 1). (2011). (2003). Reprod.

TAS2Rs are located both extracellularly on the motile cilia and on the apical membrane of the cell. The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea. J. Physiol. (2017).

Mol. This is very important because one of the challenges of using beta agonists is tachyphylaxis due to compromised functions of β2 adrenergic receptors (Beasley et al., 1999; Salpeter et al., 2010; Walker et al., 2011).

doi: 10.18632/oncotarget.8549, Zhang, C. H., Chen, C., Lifshitz, L. M., Fogarty, K. E., Zhu, M. S., and ZhuGe, R. (2012). 74:ftw004. Specifically, treatment with bitter compounds inhibited the expression of calponin, smooth muscle α-actin, and smooth muscle myosin heavy chain. While denatonium (agonist for T2R4 and T2R10) preferentially inhibits cholinergic stimulation of guinea pig trachea, chloroquine (agonist for T2R3 and T2R10) can inhibit responses initiated by a broad spectrum of contractile agonists. The proximal signaling events that ensue TAS2R activation in ASM cells are marked by increased [Ca2+]i in ASM cells. 3, 450–457. The intrinsic heterogeneity within the TAS2R receptor-agonists combinations overlaid with species-specific variations in TAS2R expression may account for some of the differences. doi: 10.1152/ajplung.00126.2012, Aoki, M., Takao, T., Takao, K., Koike, F., and Suganuma, N. (2014). Bronchodilator activity of bitter tastants in human tissue. Of particular interest, TAS2R38 expression has been reported in neutrophils by multiple investigators and has gained significant interest owing to its role in promoting antimicrobial action (Maurer et al., 2015; Gaida et al., 2016). They are often critical for maintaining homeostatic functions in various tissue systems and consequently have been targeted for drug discovery in various diseases. Med. doi: 10.1016/j.amjmed.2009.07.035, Saunders, C. J., Christensen, M., Finger, T. E., and Tizzano, M. (2014). doi: 10.1111/cbdd.12734, Keller, M., Liu, X., Wohland, T., Rohde, K., Gast, M. T., Stumvoll, M., et al. In cultured ASM cells, our studies reveal elevation in intracellular calcium concentration by a variety of bitter tastants including chloroquine, quinine and saccharine (Deshpande et al., 2010). Furthermore, in asthmatic ASM cells and lung tissue slices, neither the expression nor the signaling and function of TAS2Rs is impaired under inflammatory conditions (An et al., 2012b; Robinett et al., 2014).

J. J. Pharmacol. Methods Cell Biol. 17, 776–778. doi: 10.1002/alr.21140, PubMed Abstract | CrossRef Full Text | Google Scholar, Adler, E., Hoon, M. A., Mueller, K. L., Chandrashekar, J., Ryba, N. J., and Zuker, C. S. (2000). (2009). (2007).

Similar to epithelial cells, immune cells serve a critical function of maintaining homeostasis in tissue environments by neutralizing foreign insults. (2012). (2016).

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