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.
Highlights
G protein-coupled receptors (GPCRs) are seven transmembrane-spanning proteins that mediate cellular and physiological responses by converting extracellular stimuli into intracellular signals
TAS2R14 is expressed at comparable levels to the b1-adrenergic receptor (ADRB1), an abundantly expressed GPCR that is a critical mediator of chronotropy and ionotropy in the heart
Taste GPCRs are Regulated under Conditions of Starvation Both in vitro and in vivo Given the purported role of Tas1 GPCRs in nutrient sensing, we investigated the effect of nutrient deprivation on expression of taste receptors in cultured rat cardiomyocytes
Summary
G protein-coupled receptors (GPCRs) are seven transmembrane-spanning proteins that mediate cellular and physiological responses by converting extracellular stimuli into intracellular signals. GPCRs represent the largest receptor superfamily in the genome, recognizing and binding an array of sensory input and ligands, including photons, ions, odors/tastes, bioamines, lipids, peptides and proteins [1]. Many of the ligands for these receptors, including norepinephrine/epinephrine, endothelin and angiotensin have profound homeostatic and regulatory effects on the cardiovascular system. Mutations and modifications of GPCRs, G proteins and their regulatory partners are linked to dysfunction and disease, with an estimated 40% of all drugs on the market eliciting their activity through GPCRs [2]. Cardiovascular therapeutics are well established clinically, they target a very small fraction of cardiac-expressed GPCRs. conservative estimates are that the heart expresses upwards of 100 different nonchemosensory GPCRs, yet over 30%
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