title: Mechanism of gastric mucosal damage induced by ammonia.
abstract: The mechanism for Helicobacter pylori-induced gastric mucosal injury remains obscure. H. pylori has high urease activity to produce ammonia from urea in the stomach. In this study, the effects of ammonia on (a) gastric mucosal integrity, (b) gastric mucosal hemodynamics, (c) mucosal cellular viability, (d) mitochondrial respiration, and (e) energy metabolism of gastric mucosal were investigated. Ammonia (pH 10.3) at concentrations of greater than 125 mmol/L caused acute macroscopic gastric mucosal lesions in a dose-dependent manner, whereas glycine-NaOH buffer (pH 10.3) or ammonium chloride (pH 4.5) did not. The decrease in energy charge preceded the occurrence of gastric mucosal lesions, but ammonia caused no change in mucosal hemodynamics. Oxygen consumption of isolated cells and mitochondria of gastric mucosa was inhibited by ammonia dose-dependently. The present results indicate that ammonia impairs mitochondrial and cellular respiration and energy metabolism and that ammonia decreases mucosal cell viability, leading subsequently to mucosal damage.
authors.affiliation: Department of Medicine, Osaka University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsujii
authors.forename: S
authors.initials: S
authors.lastname: Kawano
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: H
authors.initials: H
authors.lastname: Fusamoto
authors.forename: T
authors.initials: T
authors.lastname: Kamada
authors.forename: N
authors.initials: N
authors.lastname: Sato
mesh_terms: D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000473:pathology
chemical_list: D000641:Ammonia