Sodium-Permeable Ion Channels TRPM4 and TRPM5 are Functional in Human Gastric Parietal Cells in Culture and Modulate the Cellular Response to Bitter-Tasting Food Constituents
Phil Richter, Gaby Andersen, Kristin Kahlenberg, Alina Ulrike Mueller, Philip Pirkwieser, Valerie Boger, Veronika Somoza
Abstract
High Resolution Image Download MS PowerPoint Slide Gastric parietal cells secrete chloride ions and protons to form hydrochloric acid. Besides endogenous stimulants, e.g., acetylcholine, bitter-tasting food constituents, e.g., caffeine, induce proton secretion via interaction with bitter taste receptors (TAS2Rs), leading to increased cytosolic Ca 2+ and cAMP concentrations. We hypothesized TAS2R activation by bitter tastants to result in proton secretion via cellular Na + influx mediated by transient receptor potential channels (TRP) M4 and M5 in immortalized human parietal HGT-1 cells. Using the food-derived TAS2R agonists caffeine and l -arginine, we demonstrate both bitter compounds to induce a TRPM4/M5-mediated Na + influx, with EC 50 values of 0.65 and 10.38 mM, respectively, that stimulates cellular proton secretion. Functional involvement of TAS2Rs in the caffeine-evoked effect was demonstrated by means of the TAS2R antagonist homoeriodictyol, and stably CRISPR-Cas9-edited TAS2R43ko cells. Building on previous results, these data further support the suitability of HGT-1 cells as a surrogate cell model for taste cells. In addition, TRPM4/M5 mediated a Na + influx after stimulating HGT-1 cells with the acetylcholine analogue carbachol, indicating an interaction of the digestion-associated cholinergic pathway with a taste-signaling pathway in parietal cells.