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

被引:18
|
作者
Koizumi, Shigeto [1 ]
Odashima, Masaru [1 ]
Otaka, Michiro [2 ]
Jin, Mario [1 ]
Linden, Joel [3 ]
Watanabe, Sumio [2 ]
Ohnishi, Hirohide [1 ]
机构
[1] Akita Univ, Sch Med, Dept Gastroenterol, Akita 0108543, Japan
[2] Juntendo Univ, Dept Gastroenterol, Tokyo, Japan
[3] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA USA
关键词
NSAIDs; Gastric ulcer; Adenosine A(2A) receptor; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NECROSIS-FACTOR-ALPHA; REPERFUSION INJURY; SUPEROXIDE GENERATION; LIPID-PEROXIDATION; WATER-IMMERSION; A(2B) RECEPTORS; INHIBITS IL-12; MECHANISMS; PATHOGENESIS;
D O I
10.1007/s00535-009-0028-8
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. Gastric lesions were produced by oral gavage of indomethacin (30 mg/kg). ATL-313 (1-10 mu g/kg) was given orally just before the indomethacin administration. 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 mu g/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected. 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.
引用
收藏
页码:419 / 425
页数:7
相关论文
共 50 条
  • [31] Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation
    Guo, Fangming
    Wang, Xiaohuan
    Guo, Yuanying
    Wan, Weiping
    Cui, Yanfang
    Wang, Jie
    Liu, Wenbo
    HUMAN & EXPERIMENTAL TOXICOLOGY, 2022, 41
  • [32] Adenosine Protects Against Indomethacin-Induced Gastric Damage in Rats
    Ayhan Bozkurt
    Meral Yuksel
    Goncagul Haklar
    Hizir Kurtel
    Berrak C. Yegen
    Inci Alican
    Digestive Diseases and Sciences, 1998, 43 : 1258 - 1263
  • [33] Triggering neurotrophic factor actions through adenosine A2A receptor activation: implications for neuroprotection
    Sebastiao, Ana M.
    Ribeiro, Joaquim A.
    BRITISH JOURNAL OF PHARMACOLOGY, 2009, 158 (01) : 15 - 22
  • [34] Adenosine protects against indomethacin-induced gastric damage in rats
    Bozkurt, A
    Yüksel, M
    Haklar, G
    Kurtel, H
    Yegen, BÇ
    Alican, I
    DIGESTIVE DISEASES AND SCIENCES, 1998, 43 (06) : 1258 - 1263
  • [35] Positive allosteric modulation of the adenosine A2a receptor attenuates inflammation
    Ajith A Welihinda
    Edward P Amento
    Journal of Inflammation, 11
  • [36] Positive allosteric modulation of the adenosine A2a receptor attenuates inflammation
    Welihinda, Ajith A.
    Amento, Edward P.
    JOURNAL OF INFLAMMATION-LONDON, 2014, 11
  • [37] Role of adenosine A2A receptor in the regulation of gastric somatostatin release
    Yip, L
    Kwok, YN
    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 309 (02): : 804 - 815
  • [38] Adenosine A2A receptor activation limits chronic granulomatous disease-induced hyperinflammation
    Chehata, Veronica J.
    Domeier, Phillip P.
    Weilnau, Justin N.
    Lappas, Courtney M.
    CELLULAR IMMUNOLOGY, 2011, 267 (01) : 39 - 49
  • [39] Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3receptor activation in thioglycollate-induced peritonitis
    M Carmen Montesinos
    Avani Desai
    Bruce N Cronstein
    Arthritis Research & Therapy, 8
  • [40] Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis
    Montesinos, M. Carmen
    Desai, Avani
    Cronstein, Bruce N.
    ARTHRITIS RESEARCH & THERAPY, 2006, 8 (02)