Taste receptor signaling in the mammalian gut
Section snippets
Expression of transcripts encoding members of taste receptor family of G protein coupled receptors (GPCRs) in the GI tract
A family of bitter taste receptors (referred as T2Rs), which are expressed in taste receptor cells organized within taste buds in the lingual epithelium, has been identified in humans and rodents [1, 2, 3]. These taste receptors belong to the G protein coupled receptor (GPCR) superfamily, which are characterized by seven transmembrane α-helices. Similarly, the GPCRs of the T1R family, namely T1R1, T1R2, and T1R3, have been identified as the receptors that perceive sweet substances and L-amino
Expression of the α subunits of gustducin (Gαgust) and transducin (Gαt−2) in GI cells from mouse, rat, and humans
Genetic and biochemical evidence indicate that the G protein gustducin mediates T1R and T2R signaling in the taste buds of the lingual epithelium [16], though other G proteins (e.g. transducin and Gi) are also likely to be involved in taste receptor signaling [10]. Outside the lingual epithelium, the α subunit of gustducin (Gαgust) has been localized to gastric [7••, 17•], intestinal [7••, 18•], and pancreatic [19] cells, in agreement with the notion that a taste-sensing mechanism also operates
Expression of Gαgust by endocrine cells of the GI tract
Gαgust immunoreactivity has been also detected in individual human cells distributed throughout the GI tract [8•, 14••, 23••]. Interestingly, we found that most Gαgust-positive cells co-expressed chromogranin A but not basolateral villin immunoreactivity [8•], indicating that Gαgust functions in endocrine rather than brush cells of the human GI tract. A similar conclusion was reached in two recent independent studies [14••, 23••]. Gαgust expression was detected in enteroendocrine cells but not
Expression of taste-specific markers in cultures of enteroendocrine cell lines
Cultured cell lines have been used extensively to investigate the organization, signaling pathways, and function of intestinal cells. Using RT-PCR and sequencing analysis, we demonstrated that enteroendocrine STC-1 cells express multiple T2Rs, Gαgust, phospholypase Cβ2 (PLCβ2), and transient receptor potential channel M5 (TRPM5) [6, 7••, 31•]. All these signal transduction molecules have been implicated in taste perception in the lingual epithelium. Recent studies revealed that another mouse
Signal transduction pathways activated by bitter stimuli in GI cells
The precise coupling of T1Rs, T2Rs, gustducin, PLCβ2, and TRPM5 in taste receptor cells remains incompletely understood. The βγ subunits of gustducin, transducin, and Gi are thought to stimulate PLCβ2-mediated synthesis of inositol (1,4,5)phosphate P3 (IP3) leading to the release of Ca2+ from intracellular stores, whereas Gαgust appears to reduce the intracellular level of cAMP through activation of phosphodiesterases. An increase in the intracellular Ca2+ concentration ([Ca2+]i) could trigger
Bitter and sweet agonists induce release of GI peptides in vitro and in vivo
We hypothesized that the robust increase in [Ca2+]i induced by bitter and/or sweet tastants in enteroendocrine cells triggers the release of GI peptides, including CCK, PYY, and GLP-1. These peptides activate local neural reflexes and/or vagal afferent pathways and modulate the activity of adjacent or distant target cells, including pancreatic β cells (Figure 1).
In line with this hypothesis, DB was shown to be a potent stimulant of CCK release from enteroendocrine STC-1 cells [31•]. Treatment
Conclusions and implications
Recent studies have provided striking support for the hypothesis that the molecular pathways that mediate oral taste signaling operate in specific cells of the GI tract. It is now established that taste-specific molecular transducers, including T1Rs, T2Rs, Gαgust, Gαt−2, PLCβ2, and TRPM5, are expressed by a variety of cell types interspersed in the epithelium of the mammalian GI tract [7••, 8•, 12, 15, 17•, 18•, 20, 21], including endocrine cells. These transducers are also expressed by mouse,
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The work discussed in this article was supported by National Institute of Health (NIH) Grants DK 55003, DK 56930, and DK 41301 to ER and DK54155 and Stein Oppenheimer award to CS.
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- 1
Present address: 900 Veteran Avenue, Warren Hall, Room 11-115, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1786, United States.
- 2
The Ronald S. Hirshberg Professor of Pancreatic Cancer Research.