Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart

Simon R Foster, Enzo R Porrello, Brooke W Purdue, Hsiu Wen Chan, Anja Voigt, Sabine Frenzel, Ross D. Hannan, Karen M. Moritz, David G Simmons, Peter Molenaar, Eugeni Roura, Ulrich Boehm, Wolfgang Meyerhof, Walter G. Thomas

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Abstract

G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

Original languageEnglish
Article numbere64579
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 15 May 2013
Externally publishedYes

Cite this

Foster, S. R., Porrello, E. R., Purdue, B. W., Chan, H. W., Voigt, A., Frenzel, S., ... Thomas, W. G. (2013). Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart. PLoS ONE, 8(5), [e64579]. https://doi.org/10.1371/journal.pone.0064579
Foster, Simon R ; Porrello, Enzo R ; Purdue, Brooke W ; Chan, Hsiu Wen ; Voigt, Anja ; Frenzel, Sabine ; Hannan, Ross D. ; Moritz, Karen M. ; Simmons, David G ; Molenaar, Peter ; Roura, Eugeni ; Boehm, Ulrich ; Meyerhof, Wolfgang ; Thomas, Walter G. / Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart. In: PLoS ONE. 2013 ; Vol. 8, No. 5.
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author = "Foster, {Simon R} and Porrello, {Enzo R} and Purdue, {Brooke W} and Chan, {Hsiu Wen} and Anja Voigt and Sabine Frenzel and Hannan, {Ross D.} and Moritz, {Karen M.} and Simmons, {David G} and Peter Molenaar and Eugeni Roura and Ulrich Boehm and Wolfgang Meyerhof and Thomas, {Walter G.}",
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Foster, SR, Porrello, ER, Purdue, BW, Chan, HW, Voigt, A, Frenzel, S, Hannan, RD, Moritz, KM, Simmons, DG, Molenaar, P, Roura, E, Boehm, U, Meyerhof, W & Thomas, WG 2013, 'Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart', PLoS ONE, vol. 8, no. 5, e64579. https://doi.org/10.1371/journal.pone.0064579

Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart. / Foster, Simon R; Porrello, Enzo R; Purdue, Brooke W; Chan, Hsiu Wen; Voigt, Anja; Frenzel, Sabine; Hannan, Ross D.; Moritz, Karen M.; Simmons, David G; Molenaar, Peter; Roura, Eugeni; Boehm, Ulrich; Meyerhof, Wolfgang; Thomas, Walter G.

In: PLoS ONE, Vol. 8, No. 5, e64579, 15.05.2013.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart

AU - Foster, Simon R

AU - Porrello, Enzo R

AU - Purdue, Brooke W

AU - Chan, Hsiu Wen

AU - Voigt, Anja

AU - Frenzel, Sabine

AU - Hannan, Ross D.

AU - Moritz, Karen M.

AU - Simmons, David G

AU - Molenaar, Peter

AU - Roura, Eugeni

AU - Boehm, Ulrich

AU - Meyerhof, Wolfgang

AU - Thomas, Walter G.

PY - 2013/5/15

Y1 - 2013/5/15

N2 - G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

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