Systematic survery for biologically active peptides in the atrium and pheochromocytoma tissue.

系统调查心房和嗜铬细胞瘤组织中的生物活性肽。

基本信息

批准号：
15390251
负责人：
KITAMURA Kazuo
金额：
$ 9.47万
依托单位：
University of Miyazaki (2004-2005)宮崎医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

We discovered adrenomedullin (AM) in 1993 and found another hypetensive peptide proadrenomedullin N-terminal 20 peptide (PAMP) which is produced from adrenomedullin precursor. We have clarified that AM is a new cardiovascular hormone to regulate circulation and body fluid homeostasis. Further, AM shows protective actions for the heart and blood vessels in vitro and in vivo, suggesting that AM may be a new drugs for cardiovascular and inflammatory diseases. Thus, it is important to discover the new hormone and to study its function. We have concurrently advanced the another project to discover still unidentified vasoactive peptide in the porcine atrium and human pheochromocytoma tissue.AM was discovered monitoring the activity that elevate cAMP in the rat platelet. We have searched biological active peptide using the cAMP elevation in cultured cells from pheochromocytoma. Using this assay, we isolated several peptides from pheochromocytoma tissue. These peptide were found to be VIP, PAC … More AP, CGRP and PHM. These peptides were known peptides, but we have isolated novel peptide which exist in the the pheochromocytoma. Many biologically active peptides has C-terminal amide structure which is essential for biological activity. We have established a novel method to detect a peptide with C-terminal amide structure. Using this method, we have isolated a novel 14 amino acids peptide in the atrium whose C-terminus was amidated. This peptide was termed amidicin. Amidicin is widely distributed in porcine tissue and is especially abundant in pituitary gland, cardiac ventricle and spleen. We have developed radioimmunoassay for human amidicin, and examined the distribution of amidicin in human tissue. We found that human amidicin is abundant in human pheochromocytoma tissue. We purified human amidicin from pheochromocytoma and determined its structure. Furthermore, amidicin was found to circulate in human blood in a considerable concentration. Amidicin may be a possible new peptide participating in circulation control. Less

我们于1993年发现了肾上腺髓质素（AM），并发现了另一种由肾上腺髓质素前体产生的高血压肽前肾上腺髓质素N末端20肽（PAMP），我们进一步阐明AM是一种调节循环和体液稳态的新心血管激素。在体外和体内均表现出对心脏和血管的保护作用，表明AM可能是治疗心血管和炎症疾病的新药。我们同时推进了另一个项目，即在猪心房和人嗜铬细胞瘤组织中发现尚未鉴定的血管活性肽。我们在监测大鼠血小板中发现了 AM 升高 cAMP 的活性。使用来自嗜铬细胞瘤的培养细胞中的 cAMP 升高来搜索生物活性肽，我们从嗜铬细胞瘤组织中分离出几种肽。发现的肽有VIP、PAC…更多AP、CGRP和PHM。这些肽是已知的肽，但我们分离出存在于嗜铬细胞瘤中的新肽，许多生物活性肽具有对于生物活性至关重要的C端酰胺。我们建立了一种检测具有 C 末端酰胺结构的肽的新方法，利用该方法，我们在心房中分离出了一种新的 14 个氨基酸肽。这种肽被命名为amidicin，广泛分布于猪组织中，尤其在脑垂体、心室和脾脏中含量丰富。我们开发了人amidicin的放射免疫测定法，并检测了amidicin在人体组织中的分布。我们发现人嗜铬细胞瘤组织中富含人amidicin，我们从嗜铬细胞瘤中纯化了人amidicin并确定了其结构。此外，发现Amidicin在人体血液中的浓度相当高，可能是一种参与循环控制的新肽。