Acid Suppression by Proton Pump Inhibitors Enhances Aquaporin-4 and KCNQ1 Expression in Gastric Fundic Parietal Cells in Mouse

Abstract

PPI administration increased the number of parietal cells with enhanced expression of AQP4 and KCNQ1.

Histopathologic and Immunohistochemical Characterization of Human Gastric Oxyntic Mucosa with Parietal Cell Protrusions and Investigation into the Association Between Such Mucosal Changes of the Stomach and Use of Proton Pump Inhibitors

“…The increase in the number of parietal cells and the decrease in the number of chief cells along with the disturbance in their differentiation result in the proportional change in gastric proper epithelial cells in oxyntic glands. These results are consistent with results of a recent study in lansoprazole-treated mice 4) . We observed a significant increase in the number of H+/K+-ATPase-positive cells in our PCP(+) group, which differed from the results of a recent experimental study in which the number of H+/K+-ATPase-positive cells did not differ significantly between lansoprazole-treated mice and control mice 4) .…”

“…These results are consistent with results of a recent study in lansoprazole-treated mice 4) . We observed a significant increase in the number of H+/K+-ATPase-positive cells in our PCP(+) group, which differed from the results of a recent experimental study in which the number of H+/K+-ATPase-positive cells did not differ significantly between lansoprazole-treated mice and control mice 4) . The discrepancy might be due in part to the difference between mice and humans, but the details remain unclear.…”

“…In humans, AQP4 is also expressed in chief cells 19) . Matsuzaki et al reported that distribution of AQP4-positive parietal cells in the mouse stomach toward the upper part of the glands indicates a disturbance in parietal cell differentiation 4) . AQP4-positive parietal cells tended to distribute much higher in the gland in our PCP(+) group than in our PCP(−) group.…”

“…PPIs are also used adjuvantly in the eradication of H. pylori 3) . With widespread use of PPIs came reports of gastric mucosal changes including fundic gland hyperplasia 4) , cystic dilation of fundic glands (oxyntic dilatation) 5) 6) , emergence and enlargement of socalled fundic gland polyps (FGPs) [7][8][9][10][11] , and morphologic changes in parietal cells 12) . The parietal cell protrusions (PCPs) found in patients treated with omeprazole are thought to be an especially characteristic change [13][14][15] .…”

Immunohistochemical localization of aquaporin 4 (AQP4) in the porcine gastrointestinal tract

“…In previous studies, the expression of AQP4 was detected at basolateral membrane of parietal cells located in the stomach of the rat (Fujita et al 1999), mouse (Wang et al 2000), guinea pig (Jiang et al 2014) and humans (Misaka et al 1996). Since the application of proton pump inhibitors evoking acid suppression substantially increased the number of fundic AQP4-expressing parietal cells in the mouse, the involvement of aquaporin in gastric secretory processes (acid secretion) has been postulated (Matsuzaki et al 2010). This is in line with previous findings noting a higher expression level of AQP4 in the stomach (due to increased number of AQP4-positive parietal cells) of peptide YY transgenic mice (Carmosino et al 2005).…”