Structural requirements of C-type natriuretic peptide for elevation of cyclic GMP in cultured vascular smooth muscle cells

Biochem Biophys Res Commun. 1992 Mar 31;183(3):964-9. doi: 10.1016/s0006-291x(05)80284-0.


C-type natriuretic peptide (CNP), which was recently found to be a selective ligand for one of the two known natriuretic peptide receptor guanylyl cyclases (NPR-B), potently stimulates cGMP production in cultured rat vascular smooth muscle cells (VSMC) and exerts potent antiproliferative effects on the cells. To investigate the structural requirements of CNP for stimulation of cGMP accumulation via NPR-B, we prepared CNP analogs and tested them on cultured rat VSMC. Our results indicate that only the ring portion of CNP with a disulfide bond (CNP(6-22)) participates in stimulation of cGMP accumulation, especially the sequence Leu9-Lys10-Leu11 in the ring portion executes essential roles for both elevation of cGMP and selectivity of the ligand for NPR-B. We also found a good correlation between the activities of the CNP analogs for stimulation of cGMP accumulation and inhibition of DNA synthesis.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta / cytology
  • Biological Assay
  • Cells, Cultured
  • Cyclic GMP / metabolism*
  • Male
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / metabolism*
  • Natriuretic Peptide, C-Type
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / metabolism
  • Sequence Homology, Nucleic Acid
  • Structure-Activity Relationship


  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Natriuretic Peptide, C-Type
  • Cyclic GMP