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

• Published in: Journal of gastroenterology and hepatology 2005-02, Vol.20 (2), p.275-280
• Main 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
• Format: Article
• Language: English
• Subjects: A2A receptor; adenosine; Antiarythmic agents; Biological and medical sciences; Cardiovascular system; cytokine; Medical sciences; Pharmacology. Drug treatments; stress; ulcer
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2004.03555.x

Background:  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. 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 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. 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