| Project/Area Number |
10670649
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
KITAKAZE Masafumi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20294069)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Hiroshi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10294092)
KUZUYA Tsunehiko Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (80150340)
HORI Masatsugu Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (20124779)
MIYAZAKI Jun-ichi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (10200156)
MATSUMURA Yasushi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90252642)
MINAMINO Tetsuo Osaka University Graduate School of Medicine, JSPS Research Fellow
OHTSU Kin-ya Osaka University Graduate School of Medicine, Assistant Professor (20294051)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | Myocardial Infarction / Stunning / Cardioprotection / Adenosine / Ecto-5'-Nucleotidase / Cathecolamine / Clinical Trial / 臨床試験 / 虚血・再潅流 / ccto-5^I-nuclcotidasc / 遺伝子導入 / prcconditioning現象 / 急性心筋梗塞 / ATP / protcin kinascC |
|---|
| Research Abstract |
We have previously reported that activation of protein kinase C via α 1-adrenergic stimulation activates ecto-5'-nucleotidase, which produces adenosine. Therefore, we investigated whether the activation of ecto-5'-nucleotidase plays a role in cardioprotection in vivo via the adenosine production.
First, we found that an intracoronary administration of ATP, metabolized rapidly to adenosine, reduces infarct size in canine hearts. We also establish the mice overexpressional model of ecto-5'-nucleotidase, and now under the examination on the molecular mechanisms for cardioprotection of ecto-5'-nucleotidase.
Furthermore, we are now proceeding a clinical large-scale trial named COAT study to estimate the clinical impact of adenosine on cardioprotection. We have preliminarily reported this efficacy.
Second, we found that AICA riboside, Na+/H+ exchanger inhibitors, and ATP-sensitive potassium channel openers can increase the activity of ecto-5'-nucleotidase. Since these compounds have the cardioprotective effect in canine model in vivo, we suggest the involvement of adenosine in the effects of these drugs.
Third, we established that the pretreatment with nicotine has cardioprotecitive effects against myocardial necrosis and stunning via nicotinic receptor activation, and the α1-adrenoceptor activation, which increases ecto-5'-nucleotidase activity and enhances the regional adenine production (submitted).
These basic and clinical evidence indicates the beneficial action of adenosine and ecto-5'-nucleotidase in cardiology.
|
