Details

Autor(en) / Beteiligte

• Koizumi, Shigeto
• Odashima, Masaru
• Otaka, Michiro
• Jin, Mario
• Linden, Joel
• Watanabe, Sumio
• Ohnishi, Hirohide

Titel

Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A₂A adenosine receptor in rats

Ist Teil von

• Journal of gastroenterology, 2009, Vol.44 (5), p.419-425

Ort / Verlag

Japan: Japan : Springer Japan

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 A₂A 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 A₂A 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 μg/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 A₂A receptor antagonist. The gastric content of myeloperoxidase (MPO) and proinflammatory cytokines was significantly reduced by 10 μg/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected. Conclusion We conclude that ATL-313 does not inhibit the mucosal damaging effect of indomethacin, but it does block secondary injury due to stomach inflammation. A₂A agonists may represent a class of new therapeutic drugs for NSAID-induced gastric ulcers.