Natriuretic Peptides
The cardiac natriuretic peptides (NPs) family comprises three main peptides (ANP, BNP and CNP) which are provided with properties relevant for cardiovascular and fluid homeostasis. They produce their cardiovascular and renal effects through the binding wi
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Natriuretic Peptides Massimo Volpe and Speranza Rubattu
6.1
Introduction
The natriuretic peptide (NP) family includes three well-characterized hormones, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), which play a key role in the maintenance of cardiorenal and body fluid homeostasis [1]. ANP is largely produced from cardiac atria [1], whereas BNP is predominantly secreted from the heart ventricles [1]. NPs are produced to a lesser extent in other organs, including the brain, kidney, and vessels [2]. Within the heart, they are mostly synthetized in response to increased volume overload and myocyte stress [1]. In addition, a neuroendocrine regulation of cardiac NPs involves angiotensin II, endothelin-1, and phenylephrine that, by signaling through receptors coupled to Gq proteins, increase ANP and BNP in a more gradual manner than stretch [3]. On the other hand, CNP is mainly produced by endothelial cells and is considered a noncirculating hormone [1]. In addition, urodilatin, an amino-terminal 4-amino acid extended form of ANP, is considered a renal ANP [4]. Additional components of the family, dendroaspis natriuretic peptide (DNP) and vasonatrin peptide (VNP), have been identified in the green mamba snake and in the eel [5]. ANP, BNP, and CNP derive from separate genes. ANP and BNP genes are located in the distal arm of chromosome 1 (1p36.2). Their structure is similar and includes three exons and two introns. The signal sequences are located in exon 1,
M. Volpe (*) · S. Rubattu Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy IRCCS Neuromed, Pozzilli, Italy e-mail: [email protected]; [email protected] © Springer Nature Switzerland AG 2019 M. Dorobantu et al. (eds.), Hypertension and Heart Failure, Updates in Hypertension and Cardiovascular Protection, https://doi.org/10.1007/978-3-319-93320-7_6
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whereas the coding sequences are located in exon 2; exon 3 encodes the terminal tyrosine and the 3’ untranslated region [1]. The CNP gene is located on chromosome 5 (5p13.3) and includes 13 exons [1]. NPs are synthetized as pre-prohormones and are subsequently cleaved to obtain a biologically active α-carboxy-terminal peptide along with the amino-terminal end (Fig. 6.1). Human ANP is released as a 152-amino acid pre-prohormone. After removal of the signal peptide, the proANP1–126 is released and stored into granules within the atrial cardiomyocytes. Before secretion, proANP1-126 is processed by corin, a type II transmembrane serine protease, into the circulating forms of ANP(1– 98) and of ANP(99–126). Of note, the active corin protease is obtained through the cleavage of procorin by proprotein convertase subtilisin/kexin type 6 (PCSK6) [6]. The major form of biologically active ANP is the 28-amino acid carboxy-terminal peptide, ANP(99–126). More recently, a biological functional relevance has been proven also for ANP(1–98) [7]. In addi
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