Effects of alpha-melanotropin C-terminal tripeptide analogues on macrophage NO production

Peptides. 2003 May;24(5):701-7. doi: 10.1016/s0196-9781(03)00128-1.


The C-terminal tripeptide of melanocyte-stimulating hormone, MSH (11-13) (Lys-Pro-Val), possesses strong anti-inflammatory actions, which are mediated via mechanisms that are not fully understood. To shed more light into these mechanisms we have here synthesised and evaluated the activities of L- and D-Val substituted cyclic modifications of MSH (11-13) on nitric oxide (NO) in macrophage RAW 264.7 cells, as well as on binding to melanocortin receptors (MCRs) in B16-F1 and MCR expressing insect cells, and for effects on cAMP. MSH (11-13) and its analogues did neither bind to MCRs nor stimulate cAMP in RAW 264.7 and B16-F1 cells, except H-, which showed a tendency to increase cAMP at high (10-100 microM) concentrations. However, all investigated peptides dose dependently inhibited NO in LPS/IFN-gamma-stimulated RAW 264.7, cells with a structure activity relationship suggesting the existence of a distinct receptive site. This site appears to be distinct from the MCRs and not linked with cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Cyclic AMP / biosynthesis
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Melanocyte-Stimulating Hormones / chemistry
  • Melanocyte-Stimulating Hormones / metabolism
  • Melanocyte-Stimulating Hormones / pharmacology*
  • Mice
  • Nitric Oxide / biosynthesis*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Signal Transduction
  • Stereoisomerism


  • Anti-Inflammatory Agents
  • Peptide Fragments
  • Nitric Oxide
  • MSH (11-13)
  • Melanocyte-Stimulating Hormones
  • Cyclic AMP