Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis

Noreen Orth; Philip Pirkwieser; Julia Benthin; Melanie Köhler; Sonja Sterneder; Etkin Parlar; Erika Schaudy; Jory Lietard; Timm Michel; Valerie Boger; Andreas Dunkel; Mark Somoza; Veronika Somoza

doi:10.3390/ijms26136017

Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis

Noreen Orth (First Author), Philip Pirkwieser (Co-Author), Julia Benthin (Co-Author), Melanie Köhler (Co-Author), Sonja Sterneder (Co-Author), Etkin Parlar (Co-Author), Erika Schaudy (Co-Author), Jory Lietard (Co-Author), Timm Michel (Co-Author), Valerie Boger (Co-Author), Andreas Dunkel^* (Co-Author), Mark Somoza^* (Co-Author), Veronika Somoza^* (Last Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells.

Original language	American English
Article number	6017
Journal	International Journal of Molecular Sciences
Volume	26
Issue number	13
DOIs	https://doi.org/10.3390/ijms26136017
State	Published - Jul 2025

Keywords

HGT-1 cells
TAS2Rs
atomic force microscopy
bitter taste receptors
gastric acid secretion
parietal cells
zinc

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10.3390/ijms26136017

Cite this

Orth, N., Pirkwieser, P., Benthin, J., Köhler, M., Sterneder, S., Parlar, E., Schaudy, E., Lietard, J., Michel, T., Boger, V., Dunkel, A., Somoza, M., & Somoza, V. (2025). Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis. International Journal of Molecular Sciences, 26(13), Article 6017. https://doi.org/10.3390/ijms26136017

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title = "Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis",

abstract = "The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells.",

keywords = "HGT-1 cells, TAS2Rs, atomic force microscopy, bitter taste receptors, gastric acid secretion, parietal cells, zinc",

author = "Noreen Orth and Philip Pirkwieser and Julia Benthin and Melanie K{\"o}hler and Sonja Sterneder and Etkin Parlar and Erika Schaudy and Jory Lietard and Timm Michel and Valerie Boger and Andreas Dunkel and Mark Somoza and Veronika Somoza",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

year = "2025",

month = jul,

doi = "10.3390/ijms26136017",

language = "American English",

volume = "26",

journal = "International Journal of Molecular Sciences",

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T1 - Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis

AU - Orth, Noreen

AU - Pirkwieser, Philip

AU - Benthin, Julia

AU - Köhler, Melanie

AU - Sterneder, Sonja

AU - Parlar, Etkin

AU - Schaudy, Erika

AU - Lietard, Jory

AU - Michel, Timm

AU - Boger, Valerie

AU - Dunkel, Andreas

AU - Somoza, Mark

AU - Somoza, Veronika

PY - 2025/7

Y1 - 2025/7

N2 - The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells.

AB - The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells.

KW - HGT-1 cells

KW - TAS2Rs

KW - atomic force microscopy

KW - bitter taste receptors

KW - gastric acid secretion

KW - parietal cells

KW - zinc

UR - https://www.scopus.com/pages/publications/105010329648

U2 - 10.3390/ijms26136017

DO - 10.3390/ijms26136017

M3 - Article

SN - 1661-6596

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 13

M1 - 6017

ER -

Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis

Abstract

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Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis

Abstract

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Atomic Force Microscope NanoWizard V BioScience (Bruker)

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