Studies on the processing and secretion mechanisms of atrial natriuretic peptides (ANP and BNP)

脑利钠肽(BNP)最初是从猪脑中分离出来的，后来发现它主要存在于心脏。为了研究BNP的处理途径和分泌机制，对BNP在心脏和血浆中的分子形式进行了测定。在大鼠的心脏中，BNP有两种分子形式：γ-BNP和BNP-45，在心脏的心房和心室中，ANP只以γ-ANP的形式储存。在心室中，γ-BNP是主要的分子形式，而在心房中，BNP-45是主要的分子形式。在血液中只观察到BNP-45，ANP以α-ANP的形式循环。在人类中，BNP也以两种分子形式存在：γ-BNP和BNP-32。人BNP的主要分子形式是心房的BNP-32和心室的伽马-BNP。另一方面，除了BNP-32外，人血浆中也发现了γ-BNP，并且在健康人中以主要的分子形式存在。这与人血浆中的α-ANP形成鲜明对比。这些数据表明，bi…BNP的更多合成、蛋白分解和分泌系统不同于ANP。这些差异可能反映了BNP前体的特有的mRNA结构和氨基酸序列的物种差异。我们最近对第三种利钠肽--C型利钠肽(CNP)的鉴定表明，利钠肽家族由ANP、BNP和CNP组成。为了阐明利钠肽家族的加工途径，我们确定了CNP的区域分布和内源性分子形式。在猪脑中，CNP的组织浓度最高，约为0.79pmol/g湿重，略高于BNP，约为ANP的10倍。在人脑中，CNP的浓度为1.04pmol/g湿重，约为ANP或BNP的25倍或70倍。相反，在包括心脏在内的外周组织中没有检测到显著浓度的CNP。仅在肾上腺髓质中，CNP的浓度为0.7pmol/g湿重，与ANP和BNP的情况一样。在中枢神经系统中，CNP主要以CNP-53和CNP-22的形式存在，CNP-53的浓度约为CNP-22的10倍。这些结果表明，CNP定位于中枢神经系统，其表达和加工模式受不同于ANP和BNP的调节机制。较少

Brain natriuretic peptide (BNP) was first isolated from porcine brain and then was shown to present mainly in the heart. To characterize the processing pathways and secretion mechanism of BNP, molecular forms of BNP in the heart and plasma were determined.In the case of rat, two molecular forms of BNP, gamma-BNP and BNP-45, were identified in the cardiac atrium and ventricle, where ANP is stored only as gamma-ANP. In the ventricle, gamma-BNP was a major molecular form, while BNP-45 was in the atrium. Only BNP-45 was observed in the blood stream, where ANP circulates as alpha-ANP. In human, BNP was also present as two molecular forms gamma-BNP and BNP-32. A major molecular form of human BNP was BNP-32 in the atrium and gamma-BNP in the ventricle. On the other hand, in addition to BNP-32, gamma-BNP was also identified in human plasma and gamma-BNP was present as a major molecular form in healthy subjects. This is in sharp contrast to alpha-ANP in human plasma. These data indicate that bi … More osynthesis, proteolytic processing and secretion systems of BNP are different from those of ANP. These differences may reflect the characteristic mRNA structure and species differences in the amino acid sequences of BNP precursors.Our recent identification of the third natriuretic peptide ; C-type natriuretic peptide (CNP) has revealed that the natriuretic peptide family consists of ANP, BNP and CNP. To clarify the processing pathways of the natriuretic peptide family, we determined the regional distribution and the endogenous molecular forms of CNP.In porcine brain, tissue concentration of CNP was the highest in the three natriuretic peptides at about 0.79 pmol/g wet wt., which was slightly higher than that of BNP and about 10 times higher than that of ANP. In human brain, CNP was detected at a concentration of 1.04 pmol/g wet wt., being about 25 times or 70 times higher than ANP or BNP. In contrast, a significant concentration of CNP was not detected in peripheral tissues, including heart. Only in adrenal medulla, CNP was found at a concentration of 0.7 pmol/g wet wt., as it does in the case of ANP and BNP. In the central nervous system, CNP was present mainly as CNP-53 and CNP-22 and concentration of CNP-53 was found about 10 times higher than that of CNP-22. These results indicate that CNP is localized in the central nervous system and its expresion and processing patterns are regulated bydifferent mechanisms from those of ANP and BNP.The present study shows that CNP functions as a neuropeptide in the central nervous systems, whereas ANP and BNP function as hormones in the circulating system. Less