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Selective adenosine A2A receptor agonist, ATL‐146e, attenuates stress‐induced gastric lesions in rats

ODASHIMA, MASARU, OTAKA, MICHIRO, JIN, MARIO, KOMATSU, KOGA, WADA, ISAO, MATSUHASHI, TAMOTSU, HORIKAWA, YOUHEI, HATAKEYAMA, NATSUMI, OYAKE, JINKO, OHBA, REINA, LINDEN, JOEL, WATANABE, SUMIO·2005·Journal of Gastroenterology and Hepatology
DOI 10.1111/j.1440-1746.2004.03555.x
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Abstract

Background: Activation of adenosine A 2A receptors reduces the production of various pro‐inflammatory cytokines and suppresses neutrophil activation. Water‐immersion restraint is well known to cause gastric mucosal lesions due to stress. The pathogenesis of stress‐induced gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A 2A receptors are known to be anti‐inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A 2A receptor agonist, ATL‐146e, on water‐immersion stress‐induced gastric mucosal lesions was studied. Methods: Rats were subjected to water‐immersion stress with or without pretreatment with a single intraperitoneal injection of a potent and selective agonist of the adenosine A 2A receptor. The gastric concentrations of myeloperoxidase (MPO), as an index of neutrophil accumulation, and the pro‐inflammatory cytokines, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), were measured. Results: The total length of gastric erosions (ulcer index) in control rats was 21.6 ± 3.23 mm and was reduced by 86% to 3.1 ± 0.83 mm by pretreatment with 5.0 µg/kg ATL146e (P < 0.001). The gastric content of MPO, TNF‐α and IL‐1β were all increased after water‐immersion stress and reduced to near normal levels by ATL‐146e. Conclusion: A specific adenosine A 2A agonist inhibits stress‐induced gastric inflammation and damage. A 2A agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation. © 2004 Blackwell Publishing Asia Pty Ltd

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Metadata

Authors
ODASHIMA, M., OTAKA, M., JIN, M., KOMATSU, K., WADA, I., MATSUHASHI, T., HORIKAWA, Y., HATAKEYAMA, N., OYAKE, J., OHBA, R., LINDEN, J., & WATANABE, S.
Venue
Journal of Gastroenterology and Hepatology
Publisher
Wiley
Published
2005-01-28
Volume
20
Issue
2
Pages
275-280
ISSN
  • 0815-9319
  • 1440-1746
DOI
10.1111/j.1440-1746.2004.03555.x
Cited by
14
References
0
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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