W1720 Gastric Hypersecretion Related to Cholinergic Hypersensitivity in the Flinders Rat Model of Depression Contributes to Stress Induced Ulceration of the Stomach

Abstract

G A A b st ra ct s that such gradient expression of Shh was disappeared by H. pylori colonization (J. Pathol. 206:186-197, 2005) or by hypochlorhydria due to immature parietal cells (J. Pathol. 213:161-169, 2007). The present study was designed to investigate the expression of AQP4 in the mouse stomach after acid suppression with a histamine type 2 receptor antagonist (H2RA) or proton pump inhibitor (PPI). Methods. Male 5-week-old C57B/6 mice were prepared for this study, and an H2RA (Famotidine: FAM, 15mg/kg, 2x/day, s.c.) or PPI (Lansoprasole: LPZ 30mg/kg, 1x/day, s.c.) was administered to the animals. A saline was administered as control. One, 4 or 8 weeks after the administration, the stomachs of the mice were removed and examined. The mRNA expression of AQP4 was evaluated by quantitative RT-PCR. The protein levels of AQP4 were examined by Western blotting and its localization was assessed by immunohistochemistry. Results. The LPZ group exhibited higher expression levels of the gastric AQP4 mRNA than the control or FAM group (AQP4/ β-actin: 1 week: cont. 0.77±0.05, FAM 0.75±0.05, LPZ 1.42±0.12; p<0.05; 4 weeks: cont. 0.72±0.06, FAM 0.72±0.05, LPZ 1.12±0.11; p<0.05; 8 weeks: cont. 0.73±0.05, FAM 0.65±0.03, LPZ 1.22±0.11; p<0.05). The protein level of AQP4 and Shh also exhibited higher level in LPZ group than the control or FAM group (AQP4/β-actin:% expression of control, 1 week: FAM 63.1±10.6, LPZ 203.1±22.5; p<0.01; 4 weeks: FAM 90.1±12.1, LPZ 148.9±7.9; p<0.01; 8 weeks: FAM 87.8±22.9, LPZ 134.3±18.8; p<0.01). AQP4 was specifically expressed in the basolateral membrane of the gastric parietal cells. A significant increase in the number of AQP4-positive parietal cells even in the neck of fundic glands was observed after acid suppression by LPZ. On the other hand, Shh expression was extensively reduced in LPZ group. Conclusion. Increase in the number of AQP4-positive parietal cells in the fundic glands was observed in the Shh faded area under the condition of potent acid suppression by PPI, not by H2RA. This observation suggests that the reduced proton pump activity paralleled with a faded Shh expression in basal parietal cells might determine the expression of its water channel, AQP4.