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

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 (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.

SUBMITTER: Foster SR

PROVIDER: S-EPMC3655793 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Foster Simon R SR Porrello Enzo R ER Purdue Brooke B Chan Hsiu-Wen HW Voigt Anja A Frenzel Sabine S Hannan Ross D RD Moritz Karen M KM Simmons David G DG Molenaar Peter P Roura Eugeni E Boehm Ulrich U Meyerhof Wolfgang W Thomas Walter G WG

PloS one 20130515 5

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 ...[more]

PMID: 23696900

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Project description:Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP(2)) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 x 10(-6) M; a specific ENaC blocker) and resiniferatoxin (RTX; 0-10 x 10(-6) M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic effect on the NaCl + Bz CT response, increasing the CT response between 0.25 x 10(-6) and 1 x 10(-6) M. At concentrations >1 x 10(-6) M, RTX inhibited the CT response. An increase in PIP(2) by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP(2) (a short chain synthetic PIP(2)) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP(2) by topical lingual application of phenylarsine oxide (a phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response, increased its sensitivity to RTX stimulation, and inhibited the desensitization of the CT response at RTX concentrations >1 x 10(-6) M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP(2). An increase in PIP(2) enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine) stimuli. RTX produced the same increase in the Bz-insensitive Na(+) response when present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No effect of RTX was observed on CT responses in WT mice and rats in the presence of the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 x 10(-6) M) or in TRPV1 KO mice. We conclude that PIP(2) is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP(2) seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste receptor variant, TRPV1t.

Project description:BackgroundBoth fresh and processed foods are available in the modern food environment where taste can signal presence of nutrients. However, whether these taste-nutrient relationships are maintained across different degrees of food processing is not well understood, and less is known about the relative contribution of different taste qualities to population energy intakes.ObjectivesTo investigate the association between perceived intensity of 6 taste modalities and a food's nutrient content in the context of food processing and to further examine the relative contribution of different taste clusters to total energy intakes, stratified by weight status.MethodsDiet and lifestyle data from the Singapore Multi-Ethnic Cohort Phase 2 (N = 7011; aged 21-75 y) were collected through interviewer-administrated questionnaires. Taste and nutrient profiles for each of the 269 Singaporean foods were derived using a published taste database and food composition table. Each food was then categorized into the NOVA food-processing classification (unprocessed, processed, ultra-processed) to compare the strength of taste-nutrient relationships. Multivariable-adjusted models were used to examine associations between relative consumption of foods from different taste clusters and processing categories, energy intake, and BMI (in kg/m2) within a population cohort.ResultsSweet taste and mono- and disaccharide content of foods were significantly associated across all processing categories, although this association was weaker among ultra-processed foods (UPFs) (r = 0.42) than among unprocessed foods (r = 0.72). In contrast, associations between fat sensation and fat content (r = 0.74), as well as salt taste and sodium content (r = 0.84), were stronger for UPFs. Individuals who had higher energy intakes or were overweight (BMI >23) derived significantly greater percentage of energy from processed foods rather than UPFs, and this energy was higher from "savory-fatty" and lower from "neutral" tasting foods than those with lower energy intakes and normal weight (all P < 0.001). Eighty percent of individuals' dietary energy was from both "savory-fatty" and "neutral" foods, independent of differences in total energy intake and weight status.ConclusionsTaste-nutrient relationships are maintained across different degrees of food processing. Greater consumption of foods that have a high "savory-fatty" taste was associated with increased energy intakes and overweight in the Asian population.

Dataset Information

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

Publications

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

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