Bitter Taste Receptor TAS2R43 Co-Regulates Mechanisms of Gastric Acid Secretion and Zinc Homeostasis
H. Noreen Orth, Philip Pirkwieser, Julia Benthin, Melanie Koehler, Sonja Sterneder, Etkin Parlar, Erika Schaudy, Jory Lietard, Timm Michel, Valerie Boger, Andreas Dunkel, Mark M. Somoza, Veronika SomozaThe 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.