Molecular physiology of natriuretic peptide signalling
Molecular physiology of natriuretic peptide signalling
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DOI：
10.1007/s00395-004-0460-0
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发表时间：
2004-03-01
影响因子：
9.5
通讯作者：
Kuhn, M
中科院分区：
文献类型：
--
作者：
Kuhn, M
利钠肽家族由心钠素(ANP)、B型利钠肽(BNP)和C型利钠肽(CNP)三个同源成员组成。这些小肽激活膜上特异性的鸟苷酸环化酶(GC)受体(GC-A和GC-B)，从而通过细胞内的第二信使-环GMP来调节细胞功能。自从二十多年前首次发现心钠素以来，基因打靶技术在小鼠体内的应用为研究利钠肽及其受体的分子生理和多种生物学功能提供了新的有价值的信息。GC-A和ANP基因敲除表明，这个信号系统不仅在维持正常血压和血压容量方面是必不可少的，而且在心脏本身也具有局部的、调节生长的功能。破坏编码BNP、CNP或CNP受体GC-B的基因，表明这些“利钠肽”实际上不太可能在生理上调节肾脏的钠排泄，而是可能在不同组织中发挥重要的自分泌/旁分泌cGMP介导的细胞增殖和分化作用。值得注意的是，肠肽尿鸟苷激活第三个鸟苷酸环酶(GC-C)，发挥利尿/利钠活性，以内分泌方式连接肠道和肾脏，调节肾功能，以应对口服盐负荷。本文综述了利钠肽及其鸟苷酸环化酶受体的生理学和生物化学，重点介绍了迄今为止通过靶向干扰这一多肽家族的特定成员、它们的受体或小鼠系统中的效应分子而获得的信息。
The natriuretic peptide family consists of three homologous members, atrial (ANP), B-type (BNP) and C-type natriuretic peptides (CNP). These small peptides activate specic membrane-bound guanylyl cyclase (GC) receptors (GC-A and GC-B), thus modulating cellular functions via the intracellular second messenger, cyclic GMP. Since the original discovery of cardiac ANP more than two decades ago, the application of gene targeting technology in mice has provided new valuable information regarding the molecular physiology and diverse biological functions of natriuretic peptides and their receptors. The GC-A and ANP gene knockouts demonstrated that this signalling system is not only essential in the maintenance of normal blood pressure and volume, but also has local, growth-moderating functions within the heart itself. Disruption of the genes encoding BNP, CNP or the CNP-receptor, GC-B, demonstrated that these "natriuretic peptides" are in fact unlikely to physiologically regulate renal sodium excretion but instead may exert important autocrine/paracrine cGMP-mediated effects on cellular proliferation and differentiation in different tissues. Notably, the intestinal peptide uroguanylin, which activates a third guanylyl cyclase (GC-C), exerts diuretic/natriuretic activity and links the intestine and kidney in an endocrine way to modulate renal function in response to oral salt load. Reviewed here is the physiology and biochemistry of natriuretic peptides and their guanylyl cyclase receptors, with special focus on the information gained to date from targeted disruption of specic members of this peptide family, their receptors, or effector molecules in the murine system.