Project/Area Number |
04404082
|
Research Category |
Grant-in-Aid for General Scientific Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
医学一般
|
Research Institution | Tokyo Institute of Technology |
Principal Investigator |
HIROSE Shigehisa Tokyo Institute of Technology Faculty of Bioscience and Biotechnology Professor, 生命理工学部, 教授 (10134199)
|
Co-Investigator(Kenkyū-buntansha) |
SAHEKI Toshihiko Gunma University Assistant Professor, 工学部, 助手 (00241860)
HAGIWARA Hiromi Tokyo Institute of Technology Research Center for Experimental Biology Associate, 生命理工学部, 助教授 (90189465)
|
Project Period (FY) |
1992 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥22,000,000 (Direct Cost: ¥22,000,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥8,000,000 (Direct Cost: ¥8,000,000)
|
Keywords | natriuretic peptide / receptor / subtype / endothelin / chondrocyte / cloning / oligopeptidase / オリゴペプチダーゼ / SABP / 点突然変異体 / ジスルフィド結合 / 免疫組織化学染色 / 内皮細胞 / サブタイプ / 情報伝達系 / 択一的RNAスプライシング / 分子生物学 / ウナギ / 軟骨組織 |
Research Abstract |
To further advance our understanding on the physiological significance of vasoactive peptides, we carried out the following comparative molecular biological studies on their receptors. 1) Natriuretic peptide receptors : The intra-and inter-subunit disulfide bonding pattern of the bovine and eel natriuretic peptide receptor C (NPR-C) were determined by a combination of protein sequencing and site-directed mutagenesis. Analysis of the cDNA and gene structures of mammalian NPR-C revealed the presence of an alternatively spliced mRNA species that encodes a receptor protein with a slightly modified sequence in the juxta-membrane region of the extracellular domain. A new receptor subtype, termed NPR-D,has been identified, cloned, and characterized. NPR-D has a short cytoplasmic tail and is 70% similar to the NPR-C sequence, but quite different in the tissue distribution ; NPR-D is abundant in the brain. 2)Endothelin receptors : Localization of the endothelin receptor B (ET-B) was determined by immunohistochemistry and the vascular endotherium was found to be decorated most densely. Type A endothelin receptor (ET-A) was found to be highly expressed in the perichondrium of rats and the gill epitherium of trout, suggesting that endothelin is involved in the differentiation of chondrocytes and regulation of gill functions.
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