A novel functional screening assay to monitor sweet taste receptor activation in vitro

2017 ◽  
Vol 33 (2) ◽  
pp. 173-183 ◽  
Author(s):  
Shanna Bastiaan-Net ◽  
Dianne B.P.M. van den Berg-Somhorst ◽  
Renata M.C. Ariëns ◽  
Marcel Paques ◽  
Jurriaan J. Mes
Keyword(s):  
Taste Receptor ◽  
Receptor Activation ◽  
Sweet Taste ◽  
Functional Screening ◽  
Screening Assay ◽  
Sweet Taste Receptor

scholarly journals Conserved Residues Control the T1R3-Specific Allosteric Signaling Pathway of the Mammalian Sweet-Taste Receptor

2019 ◽  
Vol 44 (5) ◽  
pp. 303-310 ◽  
Author(s):  
Jean-Baptiste Chéron ◽  
Amanda Soohoo ◽  
Yi Wang ◽  
Jérôme Golebiowski ◽  
Serge Antonczak ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Taste Receptor ◽  
Receptor Activation ◽  
Sweet Taste ◽  
Site Directed Mutagenesis ◽  
Activation Mechanism ◽  
Structural Basis ◽  
Directed Mutagenesis ◽  
Conserved Residues ◽  
Sweet Taste Receptor

Abstract Mammalian sensory systems detect sweet taste through the activation of a single heteromeric T1R2/T1R3 receptor belonging to class C G-protein-coupled receptors. Allosteric ligands are known to interact within the transmembrane domain, yet a complete view of receptor activation remains elusive. By combining site-directed mutagenesis with computational modeling, we investigate the structure and dynamics of the allosteric binding pocket of the T1R3 sweet-taste receptor in its apo form, and in the presence of an allosteric ligand, cyclamate. A novel positively charged residue at the extracellular loop 2 is shown to interact with the ligand. Molecular dynamics simulations capture significant differences in the behavior of a network of conserved residues with and without cyclamate, although they do not directly interact with the allosteric ligand. Structural models show that they adopt alternate conformations, associated with a conformational change in the transmembrane region. Site-directed mutagenesis confirms that these residues are unequivocally involved in the receptor function and the allosteric signaling mechanism of the sweet-taste receptor. Similar to a large portion of the transmembrane domain, they are highly conserved among mammals, suggesting an activation mechanism that is evolutionarily conserved. This work provides a structural basis for describing the dynamics of the receptor, and for the rational design of new sweet-taste modulators.

Non-nutritive sweetener activation of the pig sweet taste receptor T1R2-T1R3 in vitro mirrors sweetener stimulation of the gut-expressed receptor in vivo

2021 ◽  
Vol 542 ◽  
pp. 54-58
Author(s):  
Kristian Daly ◽  
Andrew W. Moran ◽  
Miran Al-Rammahi ◽  
Darren Weatherburn ◽  
Soraya P. Shirazi-Beechey
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Sweet Taste Receptor ◽  
Stimulation Of

scholarly journals Sweet Taste Receptor Activation in the Gut Is of Limited Importance for Glucose-Stimulated GLP-1 and GIP Secretion

Nutrients ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 418 ◽  
Author(s):  
Monika Saltiel ◽  
Rune Kuhre ◽  
Charlotte Christiansen ◽  
Rasmus Eliasen ◽  
Kilian Conde-Frieboes ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Receptor Activation ◽  
Sweet Taste ◽  
Sweet Taste Receptor

Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion

2013 ◽  
Vol 304 (8) ◽  
pp. G708-G714 ◽  
Author(s):  
Shingo Sato ◽  
Ryota Hokari ◽  
Chie Kurihara ◽  
Hirokazu Sato ◽  
Kazuyuki Narimatsu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Dietary Lipids ◽  
Bolus Administration ◽  
Sweet Taste Receptor ◽  
Glucagon Like Peptide ◽  
Sweetening Agents

Glucagon-like peptide-2 (GLP-2) is a potent intestinal growth factor derived from enteroendocrine L cells. Although food intake is known to increase GLP-2 secretion, its regulatory mechanisms are largely unknown as a result of its very short half-life in venules. The aims of this study were to compare the effects of luminal nutrients on the stimulation of GLP-2 secretion in vivo using lymph samples and to clarify the involvement of the sweet taste receptor in this process in vitro. Lymph samples were collected from the thoracic duct after bolus administration of dietary lipids or sweetening agents into the duodenum of rats. Human enteroendocrine NCI-H716 cells were also used to compare the effects of various nutrients on GLP-2 secretion. GLP-2 concentrations were measured by ELISA in vivo and in vitro. GLP-2 secretion was enhanced by polyunsaturated fatty acid- and monounsaturated fatty acid-rich dietary oils, dietary carbohydrates, and some kinds of sweeteners in rats; this effect was reproduced in NCI-H716 cells using α-linolenic acid (αLA), glucose, and sweeteners. GLP-2 secretion induced by sweetening agents was inhibited by lactisole, a sweetness-antagonizing inhibitor of T1R3. In contrast, lactisole was unable to inhibit GLP-2 secretion induced by αLA alone. Our results suggested that fatty acid- and sweetener-induced GLP-2 secretion may be mediated by two different pathways, with the sweet taste receptor involved in the regulation of the latter.

Isovanillic Sweeteners: Sensory Evaluation and In Vitro Assays with Human Sweet Taste Receptor

2008 ◽  
Vol 1 (3) ◽  
pp. 174-183 ◽  
Author(s):  
Angela Bassoli ◽  
Monica Laureati ◽  
Gigliola Borgonovo ◽  
Gabriella Morini ◽  
Guy Servant ◽  
...  
Keyword(s):  
Sensory Evaluation ◽  
Taste Receptor ◽  
Sweet Taste ◽  
In Vitro Assays ◽  
Sweet Taste Receptor
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