Clinical application and elucidation of significance of natriuretic peptide family

利尿钠肽家族的临床应用及意义阐明

基本信息

批准号：
01480288
负责人：
NAKAO Kazuwa
金额：
$ 4.29万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

The natriuretic peptide system consists of, at least, three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors, ANP receptor-A (guanylate cyclase A), ANP receptor-B (guanylate cyclase B) and clearance receptor (C receptor).ANP, the prototype of natriuretic peptides, is mainly produced in the atrium and secreted into the circulation as a cardiac hormone. ANP is also produced in the ventricle, and in the central nervous system. BNP first isolated from the porcine brain has a marked divergence in its molecular size and the sequence among species. In humans and rats, the major site of production of BNP is the ventricle of the heart. BNP is also secreted into the circulation as a cardiac hormone. The plasma BNP level in normal subjects is approximately one sixths of the plasma ANP level, however, the plasma BNP level markedly increases in heart failure, renal failure and hypertension and the augmentation of the BNP secretion is much larger than that of the ANP secretion. In addition, clearance of BNP from the circulation is slower than that of ANP. Furthermore, BNP is secreted more urgently than ANP in acute heart failure. CNP distributes mainly in the central nervous system and pituitary gland. No significant amount of CNP is detectable in the heart and plasma. Thus, CNP is a local regulator rather than a cardiac hormone.Three natriuretic receptors have ligand selectivity. The rank order in potency for cyclic GMP production via ANP receptor-A is ANP>BNP>>CNP, while that via ANP-B receptor is CNP>ANP>BNP. The rank-order of binding affinity for C receptor is ANP>CNP>BNP.The complicated natriuretic peptide system is implicated in the control of body fluid and blood pressure in endocrine and paracrine fashions.

利钠肽系统至少由心房利钠肽（ANP）、脑利钠肽（BNP）和C型利钠肽（CNP）三种内源性配体和三种受体组成：ANP受体-A（鸟苷酸环化酶A）、ANP受体-B（鸟苷酸环化酶B）和清除受体（C受体）。ANP是利尿钠肽的原型，主要产生于心房并作为心脏激素分泌到循环中。 ANP 也在心室和中枢神经系统中产生。首先从猪脑中分离出来的 BNP 在不同物种之间的分子大小和序列存在显着差异。在人类和大鼠中，BNP 的主要产生部位是心室。 BNP 也作为心脏激素分泌到循环中。正常人血浆BNP水平约为血浆ANP水平的六分之一，但心力衰竭、肾衰竭和高血压时血浆BNP水平显着升高，且BNP分泌的增加远大于ANP分泌的增加。此外，BNP 从循环中的清除速度比 ANP 慢。此外，在急性心力衰竭中，BNP 的分泌比 ANP 更紧急。 CNP主要分布于中枢神经系统和垂体。在心脏和血浆中未检测到显着量的 CNP。因此，CNP 是一种局部调节剂而不是心脏激素。三种利尿钠受体具有配体选择性。通过ANP受体-A产生环GMP的效力顺序为ANP>BNP>>CNP，而通过ANP-B受体产生环GMP的效力顺序为CNP>ANP>BNP。与C受体的结合亲和力顺序为ANP>CNP>BNP。复杂的利尿钠肽系统通过内分泌和旁分泌方式参与体液和血压的控制。