Colocalization of the α-subunit of gustducin with PYY and GLP-1 in L cells of human colon

Abstract

In view of the importance of molecular sensing in the function of the gastrointestinal (GI) tract, we assessed whether signal transduction proteins that mediate taste signaling are expressed in cells of the human gut. Here, we demonstrated that the alpha-subunit of the taste-specific G protein gustducin (Galpha(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 Galpha(gust) localized to enteroendocrine L cells that express peptide YY and glucagon-like peptide-1 in the human colonic mucosa. We also found expression of transcripts encoding human type 2 receptor (hT2R) family members, hT1R3, and Galpha(gust) 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, which binds hT2R38, induced a rapid increase in the intracellular Ca2+ concentration in these cells. The identification of Galpha(gust) 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.

Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers

“…And although there is some support for the involvement of TGR5 signalling in L cell stimulation [9], selective and potent non-bile salt TGR5 agonists failed to consistently stimulate L cell secretion (L. Chen, GlaxoSmithKline, Durham, NC, USA, personal communication). Other bile salt-responsive receptors potentially implicated may include one or more of the bitter receptors located on colonic L cells [10].…”

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

“…Taste receptors that respond to sweet, bitter and umami stimuli, together with their associated G-proteins have been identified within the GI mucosa co-localized with several gut peptides including ghrelin GLP-1, GIP, and CCK 88,89 . Sweet, umami and bitter-tasting stimuli are detected by members of two GPCR families, the taste 1 receptor (T1R) and taste 2-receptor family (T2R).…”

The Bitter Taste Receptor Agonist Quinine Reduces Calorie Intake and Increases the Postprandial Release of Cholecystokinin in Healthy Subjects

“…4 In the last decade, several studies have demonstrated the expression of taste receptors and their downstream signaling molecules in the gut, leading to the hypothesis that gastrointestinal taste system may play a role in the gut chemosensitivity. 5,6 In particular, studies in model cell lines 7,8 and a histochemical study 9 have shown that T2R family members are expressed by entero-endocrine cells (EECs), which constitute a first level of integration of the information coming from the lumen. 10 EECs in the gastrointestinal (GI) tract play a crucial role in the control of food intake through several ways.…”