Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions

Abstract

Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux. The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described.

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

“…All NPs are initially synthesized as preprohormones and their subsequental cleavage results in formation of biologically active 28‐amino‐acid ANP, 32‐amino‐acid BNP, and 22‐ and 53‐amino‐acid CNP 6. ANP is secreted from cardiomyocytes as active hormone, whereas BNP is secreted from cardiomyocytes as a 108‐amino‐acid prohormone (proBNP).…”

“…To date, 3 NP receptors (NPRs) have been identified, and they can be divided into 2 major classes: guanylyl cyclase‐coupled receptors A and B (GC‐A and GC‐B, or NPRA and NPRB) and a natriuretic peptide clearance receptor (NPRC) 6. NPRA and NPRB both exist as homodimers and the intracellular domain consists of a kinase homology domain, a dimerization domain, and a C‐terminal catalytic domain.…”

Effects of Aerobic Training on the Cardiomyocytes of the Right Atrium of Mice

“…The activation of these receptors leads to a reduction in preload by the elimination of water and sodium and by shifting plasma volume from intravascular to extravascular spaces 20 . The natriuretic and diuretic actions of NPR-A result from enhanced glomerular filtration and/or decreased tubular reabsorption of sodium and water, suppression of renin, aldosterone, and vasopressin secretion as well as antagonism of most of the peripheral and central effects of angiotensin II 19,21 .…”

L’ostéocrine, une nouvelle molécule de signalisation osseuse

“…À l'instar des autres PN, l'absence de résidus cystéine dans l'ostéocrine indique que les fragments agiraient comme peptides linéai-res. Les PN et, particulièrement l'ANP (atrial natriuretic peptide) et le BNP (brain natriuretic peptide), constituent d'importants régulateurs de l'homéos-tasie du tonus vasculaire par leur action natriurétique et cardiaque [6]. Il a été établi, en revanche, que le CNP exerce un rôle de régulateur local important particulièrement pour la croissance longitudinale des os longs [7,8].…”