Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats.

Abstract

AIM:

To determine whether a specific adenosine A(2A) receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines.

METHODS:

Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 mol/L, 8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5 mug/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion.

RESULTS:

Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8+/-7.75 mm and was reduced to 3.8+/-1.42 mm after pretreatment with 5.0 g/kg ATL-146e (P<0.01). The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e.

CONCLUSION:

The specific adenosine A(2A) receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

• Authors: Masaru Odashima, Michiro Otaka, Mario Jin, Koga Komatsu, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Natsumi Hatakeyama, Jinko Oyake, Reina Ohba, Sumio Watanabe, Joel Linden
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 12 Issue 4 Pg. 568-73 (Jan 28 2006) ISSN: 1007-9327 [Print] United States
• PMID: 16489670 (Publication Type: Journal Article)

Chemical References

• ATL 146e
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclohexanecarboxylic Acids
• Interleukin-1
• Purines
• Receptor, Adenosine A2A
• Tumor Necrosis Factor-alpha
• Peroxidase
• Dinoprostone
• Aspirin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (toxicity)
• Aspirin (toxicity)
• Cyclohexanecarboxylic Acids (pharmacology)
• Dinoprostone (analysis)
• Gastric Mucosa (drug effects, enzymology, metabolism, pathology)
• Interleukin-1 (analysis)
• Male
• Peroxidase (metabolism)
• Purines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Adenosine A2A (drug effects, physiology)
• Tumor Necrosis Factor-alpha (analysis)