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


CONCLUSIONS
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.
Odashima
Masaru
M
Department of Internal Medicine, Akita University of Medicine, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan.
Otaka
Michiro
M
Jin
Mario
M
Komatsu
Koga
K
Wada
Isao
I
Matsuhashi
Tamotsu
T
Horikawa
Youhei
Y
Hatakeyama
Natsumi
N
Oyake
Jinko
J
Ohba
Reina
R
Linden
Joel
J
Watanabe
Sumio
S
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced* / Q000473:pathology; D007375:Interleukin-1 / Q000031:analogs & derivatives; D008297:Male; D009195:Peroxidase / Q000032:analysis; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000517:prevention & control*; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C431129:ATL 146e; D058908:Adenosine A2 Receptor Agonists; D003509:Cyclohexanecarboxylic Acids; D007375:Interleukin-1; D011687:Purines; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase