| Project/Area Number |
15590617
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Akita University |
|---|
Principal Investigator |
WATANABE Sumio Akita University, School of Medicine, Professor, 医学部, 教授 (20138225)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OTAKA Michiro Akita University, School of Medicine, Lecturer, 医学部, 講師 (30250872)
ODASHIMA Masaru Akita University, School of Medicine, Medical doctor, 医学部, 医員 (40375267)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | Adenosine / inflammatory cytokine / サイトカイン / サイクリックAMP |
|---|
| Research Abstract |
Activation of adenosine A(2A) receptors reduces the production of various pro-inflammatory cytokines and suppresses neutrophil activation. Water-immersion restraint and aspirin are well known to cause gastric mucosal lesions. The pathogenesis of 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 and aspirin induced gastric mucosal lesions were studied. Rats were subjected to water-immersion stress and administrated aspirin 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. The gastric lesions induced by stress and NSAIDs were significantly suppressed by pretreatment of ATL-146e. The gastric content of MPO, TNF-alpha and IL-1beta were all reduced to near normal levels by ATL-146e. A specific adenosine A(2A) agonist inhibits gastric inflammation and damage. A(2A) agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation.
|
