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

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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), 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 microg/kg ATL146e (P < 0.001). The gastric content of MPO, TNF-alpha and IL-1beta 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.

• Authors: Masaru Odashima, Michiro Otaka, Mario Jin, Koga Komatsu, Isao Wada, Tamotsu Matsuhashi, Youhei Horikawa, Natsumi Hatakeyama, Jinko Oyake, Reina Ohba, Joel Linden, Sumio Watanabe
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 20 Issue 2 Pg. 275-80 (Feb 2005) ISSN: 0815-9319 [Print] Australia
• PMID: 15683432 (Publication Type: Comparative Study, Journal Article)
• Copyright: (c) 2004 Blackwell Publishing Asia Pty Ltd.

Chemical References

• ATL 146e
• Adenosine A2 Receptor Agonists
• Cyclohexanecarboxylic Acids
• Interleukin-1
• Purines
• Tumor Necrosis Factor-alpha
• Peroxidase

Topics

• Adenosine A2 Receptor Agonists
• Animals
• Cyclohexanecarboxylic Acids (pharmacology)
• Gastric Mucosa (chemistry, drug effects, pathology)
• Gastritis (chemically induced, pathology)
• Interleukin-1 (analogs & derivatives)
• Male
• Peroxidase (analysis)
• Purines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Stomach Ulcer (prevention & control)
• Stress, Physiological
• Tumor Necrosis Factor-alpha (analysis)