title: The selective ASIC3 inhibitor APETx2 alleviates gastric mucosal lesion in the rat.
abstract: This study aimed to assess the in vivo efficacy of acid sensing ion channel 3 (ASIC3) inhibitor APETx2 to alleviate acute gastric mucosal lesion (AGML) in a rat model. Thirty-six male Wistar rats were divided randomly into three groups: control group, water immersion restraint stress (WIRS) group, and APETx2 treatment group (n = 12). AGML was induced by WIRS for 6 h, and 25 microg/kg APETx2 was injected intraperitoneally before the onset of stress. Intragastric pH, ulcer index (UI) and gastric histopathological changes were measured, ASIC3 expression in thoracic dorsal root ganglia (DRG) neurons was examined by immunohistochemistry, PCR and Western blot analysis. Compared with control group, WIRS group showed obvious gastric injury with increased UI score, decreased intragastric pH and increased ASIC3 expression in DRG neurons (p < 0.05). APETx2 treatment before WIRS significantly alleviated gastric mucosal injury, decreased UI score, decreased gastric acidity and reduced ASIC3 expression in thoracic DRG neurons (p < 0.05). In conclusion, ASIC3 expression in DRG neurons projecting to the stomach is positively correlated with gastric mucosal lesion and acidosis in WIRS model. ASIC3 inhibitor APETx2 could improve gastric acidosis and alleviate AGML.
authors: Shaoqun
authors: S
authors: Xu
authors: Weifeng
authors: W
authors: Tu
authors: Junlin
authors: J
authors: Wen
authors: Hongyan
authors: H
authors: Zhou
authors: Xi
authors: X
authors: Chen
authors: Gaofeng
authors: G
authors: Zhao
authors: Qun
authors: Q
authors: Jiang
mesh_terms: D062565:Acid Sensing Ion Channels / Q000096:biosynthesis / Q000187:drug effects*; D000818:Animals; D000897:Anti-Ulcer Agents; D015153:Blotting, Western; D003064:Cnidarian Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007101:Immersion / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000897:Anti-Ulcer Agents; D003064:Cnidarian Venoms; D012313:RNA