Natriuretic peptide receptor-C signaling and regulation

Peptides. 2005 Jun;26(6):1044-59. doi: 10.1016/j.peptides.2004.09.023. Epub 2005 Apr 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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
  • Peptides / chemistry
  • Pertussis Toxin / pharmacology
  • Phosphatidylinositols / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Atrial Natriuretic Factor / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Time Factors


  • Peptides
  • Phosphatidylinositols
  • Pertussis Toxin
  • Adenylyl Cyclases
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor C