MOLECULAR-BIOLOGY OF THE NATRIURETIC PEPTIDES AND THEIR RECEPTORS
MOLECULAR-BIOLOGY OF THE NATRIURETIC PEPTIDES AND THEIR RECEPTORS
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DOI：
10.1161/01.cir.86.4.1081
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发表时间：
1992-10-01
期刊：
影响因子：
37.8
通讯作者：
GOEDDEL, DV
中科院分区：
文献类型：
--
作者：
KOLLER, KJ;GOEDDEL, DV
在过去5年对BNP和CNP的描述之后，人们对利钠肽家族的兴趣急剧增加。该激素家族受体的分子表征已经确定了受体亚型的异质性，这在药理学或生化研究中没有提及。关于ANP的生理学已经发表了很多，但BNP和CNP的主要作用仍有待阐明。一些实验表明ANP和BNP可能协同作用，特别是在心脏应激时；然而，物种间BNP结构的高度多样性以及猪BNP而非人类BNP激活人类NPR-B的能力表明，可能存在一种尚未被识别的特异性识别BNP的受体。定位研究表明，CNP是利钠肽家族中最重要的神经肽，其受体NPR-B对神经系统的限制表明，CNP和NPR-B可能在大脑中发挥作用，协调体液稳态的中心方面。在已知的三种NPRs中，有两种，即NPRs - a和NPRs - b，能够合成它们自己的第二信使cGMP。这些受体内与蛋白激酶高度同源的结构域已被证明是调节这种活性所必需的。在这些蛋白中没有检测到激酶活性，但该区域可能对ATP调节观基环化酶活性很重要。这种可能性与细胞内受体介导的cAMP信号传导有有趣的相似之处。7种跨膜受体一旦被配体激活，就与G蛋白结合，影响腺苷酸环化酶的活性。（摘要删节250字）
After the description in the past 5 years of BNP and CNP, interest in the natriuretic peptide family has dramatically increased. Molecular characterization of the receptors for this hormone family has identified a heterogeneity in the receptor subtypes not previously alluded to by pharmacological or biochemical studies. Much has been published on the physiology of ANP, but the major roles for BNP and CNP remain to be elucidated. Some experiments indicate that ANP and BNP may act synergistically, especially during cardiac stress; however, the high level of structural diversity of BNP among species and the ability of porcine BNP, but not human BNP, to activate human NPR-B suggest that an as yet unidentified receptor may exist that specifically recognizes BNP. Localization studies have implied that CNP is the most prominent neuropeptide in the natriuretic peptide family, and the restriction of its receptor, NPR-B, to the nervous system suggests that CNP and NPR-B may act in the brain to coordinate the central aspects of body fluid homeostasis. Of the three known NPRs, two, NPR-A and NPR-B, are capable of synthesizing their own second messenger, cGMP. The domain within these receptors that has high homology to protein kinases has been demonstrated to be essential for regulating this activity. No kinase activity has been measured in these proteins, but it is possible that this region is important for ATP regulation of guanylyl cyclase activity. This possibility raises interesting parallels with receptor-mediated cAMP signaling within cells. Seven transmembrane receptors, once activated by ligand, associate with G proteins to affect the activity of adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)