Natriuretic peptide receptor-C signaling and regulation

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2005-06, Vol.26 (6), p.1044-1059
• Main Author: Anand-Srivastava, Madhu B.
• Format: Article
• Language: English
• Subjects: Adenylyl cyclase; Adenylyl Cyclases - metabolism; Amino Acid Sequence; Animals; Cell Membrane - metabolism; Cytoplasm - metabolism; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Kinetics; Models, Biological; Molecular Sequence Data; Natriuretic peptides; NPR-C receptor; Peptides - chemistry; Pertussis Toxin - pharmacology; Phosphatidylinositols - chemistry; PI turnover; Protein Binding; Protein Structure, Tertiary; Receptors, Atrial Natriuretic Factor - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Time Factors
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2004.09.023

The natriuretic peptides (NP) are a family of three polypeptide hormones termed atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP regulates a variety of physiological parameters by interacting with its receptors present on the plasma membrane. These are of three subtypes NPR-A, NPR-B, and NPR-C. NPR-A and NPR-B are guanylyl cyclase receptors, whereas NPR-C is non-guanylyl cyclase receptor and is coupled to adenylyl cyclase inhibition or phospholipase C activation through inhibitory guanine nucleotide regulatory protein (Gi). ANP, BNP, CNP, as well as C-ANP 4–23, a ring deleted peptide that specifically interacts with NPR-C receptor inhibit adenylyl cyclase activity through Gi protein. Unlike other G-protein-coupled receptors, NPR-C receptors have a single transmembrane domain and a short cytoplasmic domain of 37 amino acids, which has a structural specificity like those of other single transmembrane domain receptors. A 37 amino acid cytoplasmic peptide is sufficient to inhibit adenylyl cyclase activity with an apparent Ki similar to that of ANP 99–126 or C-ANP 4–23. In addition, C-ANP 4–23 also stimulates phosphatidyl inositol (PI) turnover in vascular smooth muscle cells (VSMC) which is attenuated by dbcAMP and cAMP-stimulatory agonists, suggesting that NPR-C receptor-mediated inhibition of adenylyl cyclase and resultant decreased levels of cAMP may be responsible for NPR-C-mediated stimulation of PI turnover. Furthermore, the activation of NPR-C receptor by C-ANP 4–23 and CNP inhibits the mitogen-activated protein kinase activity stimulated by endothelin-3, platelet-derived growth factor, phorbol-12 myristate 13-acetate, suggesting that NPR-C receptor might also be coupled to other signal transduction system or that there may be an interaction of the NPR-C receptor and some other signaling pathways. In this review article, NPR-C receptor coupling to different signaling pathways and their regulation will be discussed.