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

心房钠尿肽（ANP和BNP）加工和分泌机制的研究

• 批准号: 02454510
• 负责人: KANGAWA Kenji
• 金额: $ 0.45万
• 依托单位: Miyazaki Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454510/
• 关键词: Atrial natriuretic peptide (ANP); Brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP); gamma-BNP; rat BNP-45; human BNP-32; CNP-22, -53; Processing and secretion mechanism; ラジオイムノアッセイ(RIA); CNPー22; CNPー53; 心房性ナトリウム利尿ペプチド(ANP); 脳性

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

脑钠肽（BNP）首先从猪脑中分离出来，然后被证明主要存在于心脏中。为了研究BNP的加工途径和分泌机制，本研究测定了BNP在心脏和血浆中的分子形式，在大鼠的心房和心室中发现了BNP的两种分子形式，即γ-BNP和BNP-45，其中ANP仅以γ-ANP形式储存。在心室中，γ-BNP是主要的分子形式，而BNP-45在心房中。在血流中仅观察到BNP-45，其中ANP作为α-ANP循环。在人类中，BNP也以两种分子形式γ-BNP和BNP-32存在。人BNP的主要分子形式是心房中的BNP-32和心室中的γ-BNP。另一方面，除BNP-32外，还在人血浆中鉴定出γ-BNP，并且γ-BNP作为主要分子形式存在于健康受试者中。这与人血浆中的α-ANP形成鲜明对比。这些数据表明， ...更多信息 BNP的合成、蛋白水解和分泌系统与ANP不同。这些差异可能反映了BNP前体的mRNA结构特征和氨基酸序列的物种差异。我们最近鉴定的第三种利钠肽C型利钠肽（CNP）显示，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在三种利钠肽中的组织浓度最高，约为0.79 pmol/g湿重，比BNP略高，比ANP高10倍左右。在人脑中，在1.04 pmol/g湿重浓度下检测到CNP，比ANP或BNP高约25倍或70倍。相比之下，在外周组织（包括心脏）中未检测到显著浓度的CNP。仅在肾上腺髓质中，CNP的浓度为0.7 pmol/g湿重，就像在ANP和BNP的情况下一样。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，其表达和加工方式受与ANP和BNP不同的机制调节，提示CNP在中枢神经系统中起神经肽作用，而ANP和BNP在循环系统中起激素作用。少

项目成果

J.Hino,et al.: "ISOLATION AND IDENTIFICATION OF HUMAN BRAIN NATRIURETIC PEPTIDE IN CARDIAC ATRIUM." Biochem.Biophys.Res.Commun.167. 693-700 (1990)

J.Hino 等人：“心房中人脑钠尿肽的分离和鉴定”。

N.Yokota,et al.: "INCREASED PLASMA BRAIN MATRIURETIC PEPTIDE REVELS IN DOCA-SALT HYPERTENSIVE RATS:RELATION TO BLOOD PRESSURE AND CARDIAC CONCENTRATION." Biochem.Biophys.Res.Commun.173. 632-638 (1990)

N.Yokota 等人：“多卡盐高血压大鼠血浆脑泌尿肽增加：与血压和心脏浓度的关系。”

Y. Tawaragi, K. Fuchimura, H. Nakazato, S. Tanaka, N. Minamino, K. Kangawa and H. Matsuo: "Gene and precursor structure of porcine C-type natriuretic peptide." Biochem. Biophys. Res. Commun.172. 627-632 (1990)

Y. Tawaragi、K. Fuchimura、H. Nakazato、S. Tanaka、N. Minamino、K. Kangawa 和 H. Matsuo：“猪 C 型利钠肽的基因和前体结构”。

N.Yokota,et al.: "Cardiac content of brain natriuretic peptide in DOCAーsalt hypertensive rats." Life Sci.48. 397-402 (1991)

N. Yokota 等人：“DOCA 盐高血压大鼠的心脏含量。Life Sci.48 (1991)”。

M.Kojima,et al.: "Cloning and sequence analysis of a cDNA encoding a precursor for rat Cーtype natriuretic peptide (CNP)" FEBS Lett.276. 209-213 (1990)

M. Kojima 等人：“编码大鼠 C 型钠尿肽 (CNP) 前体的 cDNA 的克隆和序列分析”FEBS Lett.209-213 (1990)。