| Project/Area Number |
09470238
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kumamoto University School of Medicine |
|---|
Principal Investigator |
TOMITA Kimio Kumamoto University, Internal Medicine, Professor, 医学部, 教授 (40114772)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NONOGUCHI Hiroshi Kumamoto University, Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (30218341)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1997: ¥6,900,000 (Direct Cost: ¥6,900,000)
|
|---|
| Keywords | endothelin / receptor antagonist / endothelin converting enzyme-1 / acute renal failure / cyclosporine, gene expression / 受容体拮抗薬 / エンドセリン交換酵素 / 受容体 |
|---|
| Research Abstract |
Endothelin-1 is thought to play a significant role in acute renal failure induced by cyclosporin A.Endothelin converting enzyme-1 (ECE-1) is a key enzyme to produce endothelin. To investigate the role of ECE-1 in the glomerular and tubular dysfunction induced by cyclosporin A, the effects of cyclosporin A on mENA and protein expression of ECE-1, prepro-ET-1, and ETA and ETB type receptor were studied. Prepro-ET-1 rapidly increased in glomeruli 30 to 60 mm. This rapid increase was followed byan increase in plasma ET-1 levels. These increases were followed by decreased expression of ECE- 1, ETA and ETB type receptor mRNA It is suggested that downregulation of glomerular and tubular ECE-1 expression may be one of defense mechanisms of ET system in acute renal failure induced by cyclosporin A.This downregulation may be caused by increased ET-1 or cyclosporin A itself. To investigate the precise mechanism of downregulation of ECE-1 mRNA, the effects of ET-1 was studied in cultured endothelial cells. Incubation of ETA for 6 hours caused a significant decrease in ECE-1 mRNA expression. This effect was was abolished by co-incubation with BQ788, a specific ETB receptor antagonist , but not by co-incubation with BQ123, a specific ETA receptor antagonist. These results suggested that ET-1 suppressed ECE-1 expression through ETB receptor, indicating the existence of a feedback mechanism of FT-1 on ECE-1 in endothelial cells.
|
