| Project/Area Number |
03404070
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
物質生物化学
|
|---|
| Research Institution | National Cardiovascular Center Research Institute (NCVCRI) |
|---|
Principal Investigator |
MATSUO Hisayuki NCVCRI, Director General, 研究所, 所長 (50028685)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MINAMINO Naoto NCVCRI, Pharmacology, Head, 薬理部, 室長 (50124839)
MIYAMOTO Kaoru NCVCRI, Bioscience, Head, バイオサイエンス部, 室長 (30125877)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥30,200,000 (Direct Cost: ¥30,200,000)
Fiscal Year 1993: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1992: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 1991: ¥15,300,000 (Direct Cost: ¥15,300,000)
|
|---|
| Keywords | Natriuretic peptide family / Atrial natriuretic peptide / Natriuretic peptide receptor / Brain natriuretic peptide / C-type natriuretic peptide / Physiological function / Molecular Biology / Gene expression / 発現調節 / 血管平滑筋細胞 / 増殖抑制 / 心疾患 / GC-B / 欠損受容体 / ナトリウム利尿ペプチド受容体 / 生体内分布 / 内因性分子型 / 血管平滑筋 |
|---|
| Research Abstract |
(1) By using gene expression system, we checked ligand selectivity and cGMP production of rat and human GC-A and GC-B receptors. Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are ligands specific to GC-A receptor, while C-type natriuretic peptide (CNP) to GC-B receptor. In rat GC-B receptor, we found non-functional receptor with binding activity. Furthermore, natriuretic peptides were shown to inhibit growth of cultured vascular smooth muscle cells as well as GC-B-expressing CHO cells.
(2) CNP has been recognized as a neuropeptide functioning in the central nervous system. By using the PCR and RIA methods, we found CNP and its mRNA in the peripheral tissue. Furthermore, significant production of CNP was detected in monocytic leukemia cell line (THP-1), when stimulated with TPA and differetiated into macrophage-like cells. These results suggest that CNP is a local regulator functioning through paracrine mode, especially in the region of arteriosclerosis or vascular injury.
(3) ANP and BNP bind to GC-A receptor and function as circulating hormones. To elucidate their functional differences, we measured peptide concentration and mRNA levels. In patients with heart failure, plasma BNP concentration increases more than 100-fold, while that of BNP decreases to less than 10% in water-deprived rats. These results suggest that BNP is an emergency hormone supporting and reinforcing the function of ANP.
|
