title: Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A2A adenosine receptor in rats.
abstract: BACKGROUND
  Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin induce gastric mucosal lesions in part by the activation of inflammatory cells and the production of proinflammatory cytokines. The activation of adenosine A(2A) receptors inhibits inflammation by increasing cyclic AMP in leukocytes and reducing both the production of various proinflammatory cytokines and neutrophil chemotaxis. The aim of present study was to determine whether administration of an orally active adenosine A(2A) receptor agonist (4-[3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-piperidine-1-carboxylic acid methyl ester; ATL-313) ameliorated indomethacin-induced gastric mucosal lesions in rats.
  
  
  METHODS
  Gastric lesions were produced by oral gavage of indomethacin (30 mg/kg). ATL-313 (1-10 microg/kg) was given orally just before the indomethacin administration.
  
  
  RESULTS
  The ulcer index induced by indomethacin was significantly (>50%) reduced by pretreatment with ATL-313 and this effect was blocked completely by the addition of equimolar ZM241385, a selective A(2A) receptor antagonist. The gastric content of myeloperoxidase (MPO) and proinflammatory cytokines was significantly reduced by 10 microg/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected.
  
  
  CONCLUSIONS
  We conclude that ATL-313 does not inhibit the mucosal damaging effect of indomethacin, but it does block secondary injury due to stomach inflammation. A(2A) agonists may represent a class of new therapeutic drugs for NSAID-induced gastric ulcers.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Koizumi
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hirohide
authors.initials: H
authors.lastname: Ohnishi