University of Queensland, School of Biomedical Sciences, Brisbane, Australia.
PLoS One. 2013 May 15;8(5):e64579. doi: 10.1371/journal.pone.0064579. Print 2013.
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.
G 蛋白偶联受体 (GPCR) 对心血管生理学至关重要。心脏细胞表达 >100 种非化学感应 GPCR,表明仍有许多重要的生理和潜在的治疗靶点有待发现。此外,人们越来越认识到,大型独特的味觉和嗅觉 GPCR 家族的成员在口腔鼻腔以外的组织中具有特定的功能,包括大脑、胃肠道和呼吸系统。迄今为止,这些化学感应 GPCR 尚未在心脏中进行系统研究。我们在啮齿动物和人类心脏组织中进行了 RT-qPCR 味觉受体筛选,结果显示离散的 2 型味觉受体 (TAS2/Tas2) 以及 Tas1r1 和 Tas1r3(组成鲜味受体)表达。这些味觉 GPCR 存在于培养的心肌细胞和成纤维细胞中,通过原位杂交可以在分离的心肌细胞中观察到整个心肌中的表达。Tas1r1 基因靶向小鼠 (Tas1r1(Cre)/Rosa26(tdRFP)) 非常准确地再现了这些数据。在出生后的发育过程中,味觉受体的表达水平受到调控。有趣的是,在饥饿后,培养的大鼠心肌细胞和体内的小鼠心脏中几种 Tas2rs 上调。味觉 GPCR 在心脏中的发现开辟了心脏研究的一个令人兴奋的新领域。我们预测这些味觉受体可能在心脏中作为营养传感器发挥作用。