Activation of the sweet taste receptor, T1r3, by the artificial sweetener sucralose regulates the pulmonary endothelium

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Brown University
  • Anglia Ruskin University

Details

Original languageEnglish (US)
Pages (from-to)L165-L176
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume314
Issue number1
StatusPublished - Jan 2018
Peer-reviewedYes

Abstract

A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin remodeling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS. The sweet taste receptor T1R3 is a G protein-coupled receptor, activated following exposure to sweet molecules, to trigger a gustducin-dependent signal cascade. In recent years, extraoral locations for T1R3 have been identified; however, no studies have focused on T1R3 within the vasculature. We hypothesize that activation of T1R3, in the pulmonary vasculature, plays a role in regulating endothelial barrier function in settings of ARDS. Our study demonstrated expression of T1R3 within the pulmonary vasculature, with a drop in expression levels following exposure to barrier-disruptive agents. Exposure of lung microvascular endothelial cells to the intensely sweet molecule sucralose attenuated LPS- and thrombin-induced endothelial barrier dysfunction. Likewise, sucralose exposure attenuated bacteria-induced lung edema formation in vivo. Inhibition of sweet taste signaling, through zinc sulfate, T1R3, or G-protein siRNA, blunted the protective effects of sucralose on the endothelium. Sucralose significantly reduced LPS-induced increased expression or phosphorylation of the key signaling molecules Src, p21-activated kinase (PAK), myosin light chain-2 (MLC2), heat shock protein 27 (HSP27), and p110α phosphatidylinositol 3-kinase (p110αPI3K). Activation of T1R3 by sucralose protects the pulmonary endothelium from edemagenic agent-induced barrier disruption, potentially through abrogation of Src/PAK/p110αPI3K-mediated cell-contact disassembly and Src/MLC2/HSP27-mediated actin remodeling. Identification of sweet taste sensing in the pulmonary vasculature may represent a novel therapeutic target to protect the endothelium in settings of ARDS.

    Research areas

  • Acute respiratory distress syndrome, Artificial sweeteners, Pulmonary endothelium, Sweet taste, T1R3

Citation formats

APA

Harrington, E. O., Vang, X. A., Braza, J., Shil, A., & Chichger, H. (2018). Activation of the sweet taste receptor, T1r3, by the artificial sweetener sucralose regulates the pulmonary endothelium. American Journal of Physiology - Lung Cellular and Molecular Physiology, 314(1), L165-L176. https://doi.org/10.1152/ajplung.00490.2016

Harvard

Harrington, EO, Vang, XA, Braza, J, Shil, A & Chichger, H 2018, 'Activation of the sweet taste receptor, T1r3, by the artificial sweetener sucralose regulates the pulmonary endothelium', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 314, no. 1, pp. L165-L176. https://doi.org/10.1152/ajplung.00490.2016