Bitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart

Foster, Simon R., Blank, Kristina, See Hoe, Louise E., Behrens, Maik, Meyerhof, Wolfgang, Peart, Jason N. and Thomas, Walter G. (2014) Bitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart. FASEB Journal, 28 10: 4497-4508. doi:10.1096/fj.14-256305

Author Foster, Simon R.
Blank, Kristina
See Hoe, Louise E.
Behrens, Maik
Meyerhof, Wolfgang
Peart, Jason N.
Thomas, Walter G.
Title Bitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2014-10-01
Year available 2014
Sub-type Article (original research)
DOI 10.1096/fj.14-256305
Open Access Status Not yet assessed
Volume 28
Issue 10
Start page 4497
End page 4508
Total pages 12
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Abstract G-protein-coupled receptors (GPCRs) are key mediators in cardiovascular physiology, yet frontline therapies for heart disease target only a small fraction of the cardiac GPCR repertoire. Moreover, there is emerging evidence that GPCRs implicated in taste (Tas1r and Tas2rs) have specific functions beyond the oral cavity. Our recent description of these receptors in heart tissue foreshadows a potential novel role in cardiac cells. In this study, we identified novel agonist ligands for cardiac-Tas2rs to enable the functional investigation of these receptors in heart tissue. Five Tas2rs cloned from heart tissue were screened against a panel of 102 natural or synthetic bitter compounds in a heterologous expression system. We identified agonists for Tas2r108, Tas2r137, and Tas2r143 that were then tested in Langendorff-perfused mouse hearts (from 8-wk-old male C57BL/6 mice). All Tas2r agonists tested exhibited concentration-dependent effects, with agonists for Tas2r108 and Tas2r137, leading to a ∼40% decrease in left ventricular developed pressure and an increase in aortic pressure, respectively. These responses were abrogated in the presence of Gαi and Gβγ inhibitors (pertussis toxin and gallein). This study represents the first demonstration of profound Tas2r agonist-induced, G protein-dependent effects on mouse heart function.
Keyword Tas2r
Cardiovascular system
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1024726
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
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Created: Sat, 05 Jul 2014, 19:02:01 EST by Simon Foster on behalf of School of Biomedical Sciences