Glucagon-like peptide-1 (GLP-1) is involved in the regulation of insulin secretion and glucose homeostasis. GLP-1 release is stimulated when berberine interacts with a novel G protein family (TAS2Rs) in enteroendocrine cells. In this study, we used STC-1 cells and examined a marked increase in Ca 2+ in response to various bitter compounds. Ca 2+ responses to traditional Chinese medicine extracts, including berberine, phellodendrine and coptisine, in STC-1 cells were suppressed by the phospholipase C (PLC) inhibitor U-73122, suggesting the involvement of bitter taste receptors in changing the physiological status of enteroendocrine cells in a PLC-dependent manner. STC-1 cells showed berberine-up-regulated preproglucagon (GLP-1 precursor) mRNA and GLP-1 secretion. A QPCR analysis demonstrated that TAS2R38, a subtype of the bitter taste receptor, was associated with GLP-1 secretion. Berberine-mediated GLP-1 secretion was attenuated in response to small interfering RNA silencing of TAS2R38. The current studies demonstrated that Gα-gustducin co-localized with GLP-1 and Tas2r106 in the STC-1 cells. We further utilized inhibitors of PLC and TRPM5, which are known to participate in taste signal transduction, to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. Berberine-induced GLP-1 release from enteroendocrine cells is modulated in a PLC-dependent manner through a process involving the activation of bitter taste receptors. Together, our data demonstrated a berberine-mediated GLP-1 secretion pathway in mouse enteroendocrine cells that could be of therapeutic relevance to hyperglycemia and the role of bitter taste receptors in the function of the small intestine.

The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca2+ intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca2+ intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca2+ concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

The tissue localization of the G protein γ-subunit Gγ13 that has been believed to be specifically expressed in taste bud before,was studied in the olfactory and vomeronasal neurons at different ages:embryonic day 15.5,postnatal days 0,5,10,21 and adult.Gγ13 appears to be a specific marker of the mature olfactory and vomeronasal neurons.In situ hybridization (ISH) reveals that Gγ13 distribution is identical to that of Gαolf,which is predominantly expressed in main olfactory epithelia (MOE),and that of Gαi2,which is predominantly expressed in mature vomeronasal organ (VNO).Gγ13 distribution differs from that of growth associated protein 43 (GAP43),and that of Gγ8.Grγ13 proteins are enriched in cilia of MOE and microvilli of VNO after P21 days.In main olfactory bulb (MOB),Gγ13-positive signals were present in the glomerular layer (GL),extemal plexiform layer (EPL) and mitral cell layer (MCL).Furthermore,the expression of Gγ13 was also detected in mitral cell layer with mRNA ISH,indicating that Gγ13 may be involved in the output of mitral cells to various parts of the olfactory cortex.In accessory olfactory bulb (AOB),the weak positive signals were also observed in the glomerular layer.In short,the current results collectively suggest that Gγ13 appear to be involved in signal transduction of MOE and VNO.

The kidney is the most important excretory organ in the body and plays an essential role in maintaining homeostasis in vivo by conserving body fluid and electrolytes and removing metabolic waste. In this study, three types of transgenic system were used to investigate the expression of the bitter taste receptor Tas2r105 in mouse renal tissue (Tas2r105-GFP/Cre, Tas2r105-GFP/Cre-DTA and Tas2r105-GFP/Cre-LacZ). The results suggest that bitter taste receptors Tas2r105 and Tas2r106 are expressed in the renal corpuscle and the renal tubule, including the proximal tubule and distal tubule. Expression of α-gustducin, an important component of taste signal transduction, was also detected in mouse kidney. Meanwhile, conditional diphtheria toxin (DTA) expression in Tas2r105+ cells caused an increase in size of the glomerulus and renal tubule, accompanied by a decrease in cell density in the glomerulus. This indicates that Tas2r105+ cells play an important role in maintaining the structure of the glomerulus and renal tubules. Overall, the current study collectively demonstrates that cells labeled by bitter taste receptor expression may play a critical role in controlling human health, and have properties far beyond the original concept of taste perception.

The small intestine is the most important digestion and absorption organ in the body. Taste receptors and taste signal transduction cascades were detected in a variety of non-lingual tissues including testis, kidney, nasal cavity, lung, heart and gastrointestinal (GI) tract. Though the expression of bitter taste receptors and taste signal transduction cascades has been reported in the gut for a decade, the evidence revealing the expression of Tas2rs in the gut remain unbelievable. Here, the amplification of 35 bitter taste receptors from small intestine cDNA revealed that all transcripts are present in duodenum, jejunum and ileum, except Tas2r117. In addition, Tas2Rs and taste-related signaling transduction cascades are also observed in mouse small intestine including duodenum, jejunum and ileum by RT-PCR and Western Blot. On the other hand, three types of transgenic system were used to investigate the expression of the bitter taste receptor Tas2r105 in mouse intestine (Tas2r105-GFP/Cre, Tas2r105-GFP/Cre-DTA and Tas2r105-GFP/Cre-LacZ). With the bitter taste receptor mTas2r105 transgenic mice, the expression of mTas2r105 is showed in the villus and crypts of small intestine. mTas2r105 positive cells are also observed at the connective tissue of villus. DTA expression in mTas2r105 + cells completely ablate the expression of mTas2r105 in intestinal epithelia, but did not ablate mTas1r3 expression in intestine epithelia. LacZ staining further reveals that bitter taste receptor mTas2r105 is expressed in crypt base cells.