Effects of alpha-melanotropin C-terminal tripeptide analogues on macrophage NO production.
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.
Muceniece
Ruta
R
Faculty of Medicine, University of Latvia, Sarlotes iela 1a, LV-1001 Riga, Latvia. rutam@latnet.lv
Krigere
Liga
L
Süli-Vargha
Helga
H
Wikberg
Jarl E S
JE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction; D013237:Stereoisomerism
D000893:Anti-Inflammatory Agents; D010446:Peptide Fragments; D009569:Nitric Oxide; C043156:MSH (11-13); D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP