title: Role of endogenous nitric oxide synthase inhibitor in gastric mucosal injury.
abstract: To explore the role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in gastric mucosal injury, 3 models of gastric mucosal injury induced by ethanol, indomethacin, or cold stress were used in rats. The cultured human gastric mucosal epithelial cell line GES-1 infected by Helicobacter pylori (Hp) was selected to mimic human gastric mucosal injury. Gastric mucosal ulcer index (UI), levels of ADMA and NO, and activity of dimethylarginine dimethylaminohydrolase (DDAH) were determined in the mucosal injury models; in Hp-infected or ADMA-treated GES-1 cells, levels of ADMA, NO, and TNF-alpha and activity of DDAH were measured. The results showed that UI and levels of ADMA were markedly increased and accompanied by significantly decreased DDAH activity in the mucosal injury models. Incubation of GES-1 cells with Hp increased levels of TNF-alpha and ADMA and decreased activity of DDAH. Administration of ADMA also increased levels of TNF-alpha. The results suggest that ADMA plays an important role in facilitating gastric mucosal injury, an effect which is associated with inhibiting NO synthesis and inducing inflammatory reaction.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No.110 Xiang-Ya Road, Changsha 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: De-Jian
authors.initials: DJ
authors.lastname: Jiang
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology / Q000633:toxicity; D016123:Campylobacter jejuni / Q000254:growth & development; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000382:microbiology; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries; D016480:Helicobacter pylori / Q000254:growth & development; D006801:Humans; D007213:Indomethacin / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000431:Ethanol; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D007213:Indomethacin