Skip to main content

Main menu

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Archive
    • Subject Collections
    • Special Collections
  • Reviews & Opinions
    • Editorials
    • Research News
    • Essays
    • Commentaries
    • Perspectives
    • Milestones in Physiology
    • Reviews
    • Viewpoints
  • Alerts
  • About
    • About JGP
    • History
    • Editors & Staff
    • Permissions & Licensing
    • Advertise
    • Contact Us
    • Privacy Policy
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Publication Fees
    • Author Services
  • Subscriptions
  • Rockefeller University Press
  • JCB
  • JEM
  • JGP
  • LSA

User menu

  • Log in

Search

  • Advanced search
JGP
  • Rockefeller University Press
  • JCB
  • JEM
  • JGP
  • LSA
  • Log in
JGP

Advanced Search

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Archive
    • Subject Collections
    • Special Collections
  • Reviews & Opinions
    • Editorials
    • Research News
    • Essays
    • Commentaries
    • Perspectives
    • Milestones in Physiology
    • Reviews
    • Viewpoints
  • Alerts
  • About
    • About JGP
    • History
    • Editors & Staff
    • Permissions & Licensing
    • Advertise
    • Contact Us
    • Privacy Policy
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Publication Fees
    • Author Services
  • Subscriptions

You are here

jgp Home » 2017 Archive » 1 February » 149 (2): 181
Review

Extraoral bitter taste receptors in health and disease

Ping Lu, View ORCID ProfileCheng-Hai Zhang, Lawrence M. Lifshitz, Ronghua ZhuGe
Ping Lu
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cheng-Hai Zhang
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cheng-Hai Zhang
Lawrence M. Lifshitz
Biomedical Imaging Group, University of Massachusetts Medical School, Worcester, MA 01605Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronghua ZhuGe
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605Biomedical Imaging Group, University of Massachusetts Medical School, Worcester, MA 01605
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1085/jgp.201611637 | Published January 4, 2017
  • Article
  • Figures & Data
  • Info
  • Metrics
  • Preview PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    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.
    • Download figure
    • Open in new tab
    • Download powerpoint
    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.
    • Download figure
    • Open in new tab
    • Download powerpoint
    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.
    • Download figure
    • Open in new tab
    • Download powerpoint
    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

  • Figures
    • View popup
    Table 1. T2R-associated disorders and diseases
    T2R typeAffected systemEffectsReference
    T2R38Human upper respiratory systemT2R38 genotype is correlated with susceptibility, severity, and prognosis of chronic rhinosinusitis, as well as biofilm formation in chronic rhinosinusitis patientsLee et al., 2012; Lee and Cohen, 2013; Adappa et al., 2014, 2016a,b,c
    Human colorectal cancerT2R38 nonfunctional group has an increased risk of colorectal cancer in a population of Caucasian originCarrai et al., 2011
    Human gingivaT2R38 genotype is associated with gingival innate immunity and the risk of dental cariesWendell et al., 2010; Gil et al., 2015
    Human colonic mucosaIncreased number of T2R38 immunoreactive cells in overweight and obese subjectsLatorre et al., 2016
    T2R19Blood glucoseT2R19 haplotype is associated with altered glucose and insulin homeostasisDotson et al., 2008
    T2R50Human heartT2R50 SNPs (ID rs1376251) have a strong association with cardiovascular diseaseShiffman et al., 2008
    T2R42ThyroidThyroid-expressed T2R42 SNP (SNP type L196F) is associated with differences in circulating levels of thyroid hormonesClark et al., 2015
    T2R16LongevityAn upstream position polymorphism of T2R16 is significantly associated with longevityCampa et al., 2012
    T2RsHuman leukocytes10 T2Rs are up-regulated in leukocytes in severe asthma patientsOrsmark-Pietras et al., 2013
    T2RsHuman Parkinson’s disease patients’ brainsT2R5 and T2R50 are decreased, whereas T2R10 and T2R13 are augmented at both premotor and parkinsonian stages in the frontal cortex areaGarcia-Esparcia et al., 2013
    Human schizophrenia patients’ brainsT2R4, T2R5, T2R14, and T2R50 are down-regulated in the dorsolateral prefrontal cortexAnsoleaga et al., 2015
    T2R4Human breast cancerT2R4 is down-regulated in breast cancer cellsSingh et al., 2014
    T2R105Mouse testesDepletion of T2R105 results in smaller testes and leads to male infertilityLi and Zhou, 2012
    Mouse glomerulus and renal tubuleAblation of T2R105-positive cells causes an increase in the size of the glomerulus and renal tubule and a lower cell density in the glomerulusLiu et al., 2015
    T2R126, T2R135, and T2R143Mouse heartStarvation increases the expression of these T2Rs by two- to threefoldFoster et al., 2013
Previous articleNext article
Back to top
Download PDF
Citation Tools
Extraoral bitter taste receptors in health and disease
Ping Lu, Cheng-Hai Zhang, Lawrence M. Lifshitz, Ronghua ZhuGe
The Journal of General Physiology Feb 2017, 149 (2) 181-197; DOI: 10.1085/jgp.201611637

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts
Sign In to Email Alerts with your Email Address

Email logo Twitter logo Facebook logo Mendeley logo Reddit logo CiteULike logo LinkedIn logo
The Journal of General Physiology: 151 (2)

Current Issue

February 4, 2019
Volume 151, No. 2

  • Table of Contents
  • All Issues

Jump To

  • Article
    • Abstract
    • ACKNOWLEDGMENTS
    • Footnotes
    • References
  • Figures & Data
  • Info
  • Metrics
  • Preview PDF
 

Subjects

  • Signal Transduction
  • Pathophysiology

ARTICLES

  • Current Issue
  • Newest Articles
  • Archive
  • Alerts
  • RSS feeds

FOR AUTHORS

  • Submit a Manuscript
  • Instructions for Authors

ABOUT

  • About JGP
  • Editors & Staff
  • Permissions & Licensing
  • Advertise
  • Feedback
  • Newsroom
  • Privacy Policy

CONNECT WITH JGP

  • Email
  • Facebook
  • Twitter
  • RSS
  • Instagram

Online ISSN: 1540-7748
Print ISSN: 0022-1295

Copyright © 2019 JGP by Rockefeller University Press