Article Figures & Data
Figures
- Figure 1.
The canonical T2R signaling pathway. (A) The invariant portion of T2R-mediated signaling in the tongue and extraoral cells/tissues includes bitter compounds binding (outside the cell; not depicted) with the receptors to increase intracellular calcium. (B) The remaining components of the T2R pathway in the taste bud.
- Figure 2.
The cell-autonomous model of the T2R signaling cascade. (A) Bitter tastants increase cilia beat frequency in airway epithelium. (B) Bitter tastants relax precontracted airway smooth muscle cells. cGMP, cyclic guanosine monophosphate.
- Figure 3.
The paracrine model of the T2R signaling cascade. (A) In the gut, dietary toxins or bitter compounds from bacteria activate T2Rs in EECs to release the peptide hormone CCK, which acts through CKK2 receptors in the neighboring enterocytes to promote ABCB1 to pump bitter-tasting toxins out of the enterocytes (right). Alternatively, CCK released by EECs can also activate CCK1 receptors on sensory fibers of the vagus nerve to send signals to the brain to limit food intake (left). (B) The paracrine model also operates in mouse SCCs from the nasal organ or VNO and in brush cells from the trachea and bladder, where bitter compounds or N-acyl homoserine lactones, bacterial quorum-sensing molecules, activate bitter-taste signaling to release Ach, which in turn activates sensory fibers to (a) initiate a protective reflex, leading to a decrease in respiratory rate or an increase in bladder contraction; (b) close the VNO duct; or (c) induce neurogenic inflammation in the nasal cavity. (C) In tuft cells from the gut, parasites activate the canonical taste cascade and release IL-25, which in turn increases the number of ILC2s and boosts the secretion of type 2 immune cytokines IL-13 and IL-4; these cytokines subsequently promote the hyperplasia of tuft cells and goblet cells.
- Figure 4.
The endocrine model of the T2R signaling pathway in EECs. These cells secrete GLP-1, which diffuses across the extracellular fluids to enter the circulation, and in turn stimulate the release of insulin from pancreatic β-cells.
Tables
T2R type Affected system Effects Reference T2R38 Human upper respiratory system T2R38 genotype is correlated with susceptibility, severity, and prognosis of chronic rhinosinusitis, as well as biofilm formation in chronic rhinosinusitis patients Lee et al., 2012; Lee and Cohen, 2013; Adappa et al., 2014, 2016a,b,c Human colorectal cancer T2R38 nonfunctional group has an increased risk of colorectal cancer in a population of Caucasian origin Carrai et al., 2011 Human gingiva T2R38 genotype is associated with gingival innate immunity and the risk of dental caries Wendell et al., 2010; Gil et al., 2015 Human colonic mucosa Increased number of T2R38 immunoreactive cells in overweight and obese subjects Latorre et al., 2016 T2R19 Blood glucose T2R19 haplotype is associated with altered glucose and insulin homeostasis Dotson et al., 2008 T2R50 Human heart T2R50 SNPs (ID rs1376251) have a strong association with cardiovascular disease Shiffman et al., 2008 T2R42 Thyroid Thyroid-expressed T2R42 SNP (SNP type L196F) is associated with differences in circulating levels of thyroid hormones Clark et al., 2015 T2R16 Longevity An upstream position polymorphism of T2R16 is significantly associated with longevity Campa et al., 2012 T2Rs Human leukocytes 10 T2Rs are up-regulated in leukocytes in severe asthma patients Orsmark-Pietras et al., 2013 T2Rs Human Parkinson’s disease patients’ brains T2R5 and T2R50 are decreased, whereas T2R10 and T2R13 are augmented at both premotor and parkinsonian stages in the frontal cortex area Garcia-Esparcia et al., 2013 Human schizophrenia patients’ brains T2R4, T2R5, T2R14, and T2R50 are down-regulated in the dorsolateral prefrontal cortex Ansoleaga et al., 2015 T2R4 Human breast cancer T2R4 is down-regulated in breast cancer cells Singh et al., 2014 T2R105 Mouse testes Depletion of T2R105 results in smaller testes and leads to male infertility Li and Zhou, 2012 Mouse glomerulus and renal tubule Ablation of T2R105-positive cells causes an increase in the size of the glomerulus and renal tubule and a lower cell density in the glomerulus Liu et al., 2015 T2R126, T2R135, and T2R143 Mouse heart Starvation increases the expression of these T2Rs by two- to threefold Foster et al., 2013
Current Issue
September 4, 2017
Volume 149, No. 9