Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart

TY - JOUR

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

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

N1 - Voigt für: German Inst Human Nutr DIfE Potsdam Rehbruecke, Dept Mol Genet, Nuthetal, Germany

PY - 2013/1/1

Y1 - 2013/1/1

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 (Tas1r1(Cre)/Rosa26(tdRFP)) 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.

AB - 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 (Tas1r1(Cre)/Rosa26(tdRFP)) 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.

KW - Animals

KW - Fibroblasts

KW - Gene Expression Regulation

KW - Humans

KW - Mice

KW - Myocardium

KW - Myocytes, Cardiac

KW - Physical Chromosome Mapping

KW - Rats

KW - Receptors, G-Protein-Coupled

KW - Starvation

KW - Taste

U2 - 10.1371/journal.pone.0064579

DO - 10.1371/journal.pone.0064579

M3 - SCORING: Journal article

C2 - 23696900

VL - 8

SP - e64579

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 5

ER -