Molecular Biology of the Natriuretic Peptide System

Abstract

The natriuretic peptides (NPs) are a group of peptide hormones that play important roles in the control of renal, cardiovascular, endocrine, and skeletal homeostasis. Atrial NP (ANP) was first identified as an activity by de Bold et al1 in 1981. It is a 28 amino acid peptide in humans that assumes a hairpin structure by virtue of a cystine bridge that links residues 7 and 23 (Figure 1). Brain NP (BNP), also known as the B-type NP, is 32 amino acids long in the human. It has a similar hairpin structure but demonstrates considerably more heterogeneity across species than ANP. C-type NP (CNP) is a 22 amino acid peptide that has a truncated carboxy terminus beyond the second cystine residue in the bridge. Figure 1. Primary structure of human NPs. ANP and BNP are produced primarily within the muscle cells of the heart. ANP shows a preference for expression in the cardiac atria versus ventricle, whereas BNP is more equivalently expressed throughout the heart. ANP is also expressed in the hypothalamus where it is thought to control blood pressure (BP), sympathetic outflow, vasopressin secretion, drinking behavior, and cardiovascular homeostasis. BNP, on the other hand, is expressed in the brains of only a few species (eg, pig and dog), where its function remains unknown. CNP is expressed in the central nervous system, reproductive tract, bone, and endothelium of blood vessels. There are 3 different types of NP receptors, and each of them spans the membrane bilayer as a single transmembrane segment. The type A NP receptor (NPR-A) is also known as the particulate guanylyl cyclase A. It is the high affinity receptor for both ANP and BNP. A schematic of the structure of this receptor is presented in Figure 2. NPR-A has a glycosylated, extracellular, ligand-binding domain linked to …