6533b82dfe1ef96bd1291eda
RESEARCH PRODUCT
Effects of alpha-melanotropin C-terminal tripeptide analogues on macrophage NO production.
Ruta MucenieceRuta MucenieceJarl E. S. WikbergLiga KrigereHelga Süli-varghasubject
PhysiologyAnti-Inflammatory AgentsTripeptideBiologyNitric OxideBiochemistryNitric oxideCellular and Molecular Neurosciencechemistry.chemical_compoundMiceEndocrinologyCell Line TumorCyclic AMPStructure–activity relationshipAnimalsMelanocyte-Stimulating HormonesBinding siteReceptorBinding SitesMacrophagesStereoisomerismPeptide FragmentschemistryBiochemistryCell cultureMelanocortinSignal transductionSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-08-05 | Peptides |