Human Sweet Receptor T1R3 is Functional in Human Gastric Parietal Tumor Cells (HGT-1) and Modulates Cyclamate and Acesulfame K-Induced Mechanisms of Gastric Acid Secretion.

Abstract

The noncaloric sweeteners (NCSs) cyclamate (Cycl) and acesulfame K (AceK) are widely added to foods and beverages. Little is known about their impact on gastric acid secretion (GAS), which is stimulated by dietary protein and bitter-tasting compounds. Since Cycl and AceK have a bitter off taste in addition to their sweet taste, we hypothesized they modulate mechanisms of GAS in human gastric parietal cells (HGT-1). HGT-1 cells were exposed to sweet tastants (50 mM of glucose, d-threonine, Cycl, or AceK) and analyzed for their intracellular pH index (IPX), as an indicator of proton secretion by means of a pH-sensitive dye, and for mRNA levels of GAS-associated genes by RT-qPCR. Since the NCSs act via the sweet taste-sensing receptor T1R2/T1R3, mRNA expression of the corresponding genes was analyzed in addition to immunocytochemical localization of the T1R2 and T1R3 receptor proteins. Exposure of HGT-1 cells to AceK or d-threonine increased the IPX to 0.60 ± 0.05 and 0.80 ± 0.04 ( P ≤ 0.05), respectively, thereby indicating a reduced secretion of protons, whereas Cycl demonstrated the opposite effect with IPX values of -0.69 ± 0.08 ( P ≤ 0.05) compared to controls (IPX = 0). Cotreatment with the T1R3-inhibitor lactisole as well as a TAS1R3 siRNA knock-down approach reduced the impact of Cycl, AceK, and d-thr on proton release ( P ≤ 0.05), whereas cotreatment with 10 mM glucose enhanced the NCS-induced effect ( P ≤ 0.05). Overall, we demonstrated Cycl and AceK as modulators of proton secretion in HGT-1 cells and identified T1R3 as a key element in this response.

• Authors: Muhammet Zopun, Kathrin I Liszt, Verena Stoeger, Maik Behrens, Ulrike Redel, Jakob P Ley, Joachim Hans, Veronika Somoza
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 66 Issue 19 Pg. 4842-4852 (May 16 2018) ISSN: 1520-5118 [Electronic] United States
• PMID: 29665689 (Publication Type: Journal Article)

Chemical References

• Cyclamates
• Receptors, G-Protein-Coupled
• Sweetening Agents
• Thiazines
• taste receptors, type 1
• acetosulfame

Topics

• Cell Line, Tumor
• Cyclamates (metabolism)
• Gastric Acid (metabolism)
• Humans
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Sweetening Agents (metabolism)
• Thiazines (metabolism)