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- Title
Selective adenosine A<sub>2A</sub> receptor agonist, ATL-146e, attenuates stress-induced gastric lesions in rats.
- Authors
ODASHIMA, MASARU; OTAKA, MICHIRO; JIN, MARIO; KOMATSU, KOGA; WADA, ISAO; MATSUHASHI, TAMOTSU; HORIKAWA, YOUHEI; HATAKEYAMA, NATSUMI; OYAKE, JINKO; OHBA, REINA; LINDEN, JOEL; WATANABE, SUMIO
- Abstract
Activation of adenosine A2A 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 A2A 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 A2A receptor agonist, ATL-146e, on water-immersion stress-induced gastric mucosal lesions was studied.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 A2A 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.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.A specific adenosine A2A agonist inhibits stress-induced gastric inflammation and damage. A2A agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation.© 2004 Blackwell Publishing Asia Pty Ltd
- Subjects
ULCER treatment; ADENOSINES; CYTOKINES; GASTRIC mucosa; PHYSIOLOGICAL stress; LABORATORY rats; WOUNDS &; injuries
- Publication
Journal of Gastroenterology & Hepatology, 2005, Vol 20, Issue 2, p275
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2004.03555.x