The Pharmacology of Taste by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783031064500
Publisher: Springer International Publishing

2 Extraoral Expression of T2Rs

Studies in the recent years have highlighted the expression of T2Rs in several extraoral tissues including gut, brain, cancer cells, and endometrium, which are briefly reviewed in this section. For more comprehensive discussion on extraoral roles of T2Rs, readers are referred to one of our earlier reviews (Shaik et al. 2016) and accompanying chapters in this book.

2.1 T2Rs in Brain, Gut, and Cancers

The first study to suggest expression of TAS2Rs in brain cells was pursued in rats (Singh et al. 2011). This study showed by RT-PCR and immunohistochemistry analysis that TAS2R4, TAS2R107, and TAS2R38 were expressed in rat brain stem, cerebellum, cortex, and nucleus accumbens (Singh et al. 2011). After this study, there were reports of TAS2R expression in brain tissues of both animal models and humans but the functional role of these T2Rs in these tissues remains to be understood and characterized. The human fundic primary cells were shown to express T2R10 and its activation was shown to influence ghrelin secretion (Wang et al. 2019), TAS2R5 and TAS2R38 were detected in human duodenal sections and enteroendocrine cells (EEC) responsible for secreting anorexigenic peptides such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) (Park et al. 2015; Latorre et al. 2016). Studies have shown increased secretion of GLP-1 and PYY hormones in NCI-H716 cells upon treatment with T2R5 agonist 1,10-phenantroline (Park et al. 2015). The GLP-1 and PPY secretion was decreased upon downregulation of α-gustducin and multiple T2Rs (Kim et al. 2014). TAS2R3, TAS2R4, and TAS2R10 along with their downstream signal transducing partners are expressed in the human gastric smooth muscle cells (Avau et al. 2015). The presence of T2Rs in the brain and gut suggests their involvement in neuroendocrine systems; gut–brain feedback systems and the regulation of energy homeostasis. Recently, a study has shown that intra-gastric administration of quinine resulted in the enhanced brain activity in the hypothalamus and the hedonic regions (Iven et al. 2019). In contrast, decreased plasma levels of octanoylated ghrelin, total ghrelin, and motilin hormones were observed in subjects treated with quinine versus placebo leading to decreased hedonic food intake (Iven et al. 2019). Several questions have been raised about the role of T2Rs in obesity and fat tissue differentiation. T2R38 was shown to be expressed in human adipocytes and was found to be highly expressed in obese subjects as compared to the lean subjects (Cancello et al. 2020). The same study also showed T2R38 to be responsible for adipocyte differentiation and delipidation (Cancello et al. 2020).

Recent studies suggest the expression of T2Rs in many cancers including breast, pancreatic, neuroblastoma, prostate and ovarian cancers (Gaida et al. 2016b; Seo et al. 2017; Martin et al. 2019; Singh et al. 2020). However, the pathophysiological role of T2Rs in these cancers is varied and not fully understood. The tissue biopsies from pancreatic ductal adenocarcinoma patients and membrane preparations from Su8686 and HuH7 cell lines revealed co-localization of T2R38 with a lipid droplet marker perlin (Gaida et al. 2016b). In another

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