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subunit of gustducin with PYY and GLP-1 in L cells of human colon
1 Medicine, UCLA, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: erozengurt{at}mednet.ucla.edu.
In view of the importance of molecular sensing in the function of the GI tract, we assessed whether signal transduction proteins that mediate taste signaling are expressed in cells of the human gut. Here, we demonstrate that the a subunit of the taste-specific G protein gustducin (G
gust) is expressed prominently in cells of the human colon that also contain chromogranin A, an established marker of endocrine cells. Double-labeling immunofluorescence and staining of serial sections demonstrated that Ggust localizes to enteroendocrine L cells that express PYY and GLP-1 in the human colonic mucosa. We also found expression of transcripts encoding human type 2 receptor (hT2R) family members, hT1R3 and Ggust in the human colon and in the human intestinal endocrine cell lines HuTu-80 and NCI-H716 cells. Stimulation of HuTu-80 or NCI-H716 cells with the bitter-tasting compound phenylthiocarbamide (PTC) that binds hT2R38, induced a rapid increase in the intracellular Ca2+ concentration in these cells. The identification of Ggust and chemosensory receptors that perceive chemical components of ingested substances, including drugs and toxins, in open enteroendocrine L cells has important implications for understanding molecular sensing in the human GI tract and for developing novel therapeutic compounds that modify the function of these receptors in the gut.
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