β- and γ-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain

• Published in: Brain research 2004-01, Vol.995 (1), p.7-13
• Main Authors: Muceniece, Ruta, Zvejniece, Liga, Kirjanova, Olga, Liepinsh, Edgars, Krigere, Liga, Baumane, Larisa, Kalvinsh, Ivars, Wikberg, Jarl E.S., Dambrova, Maija
• Format: Article
• Language: English
• Subjects: alpha-MSH - metabolism; alpha-MSH - pharmacology; alpha-MSH/metabolism/pharmacology; Animals; beta-MSH - metabolism; beta-MSH - pharmacology; beta-MSH/metabolism/pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Brain inflammation; Brain/drug effects/metabolism/physiopathology; Disease Models, Animal; Dose-Response Relationship, Drug; Electron paramagnetic resonance; Electron Spin Resonance Spectroscopy; Feedback, Physiological - drug effects; Feedback, Physiological - physiology; Fundamental and applied biological sciences. Psychology; gamma-MSH - metabolism; gamma-MSH - pharmacology; gamma-MSH/metabolism/pharmacology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Inflammation Mediators - metabolism; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Male; Melanocortin; Mice; Mice, Inbred ICR; Nitric oxide; Nitric Oxide - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Signal Transduction/drug effects/physiology; Vertebrates: endocrinology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2003.09.039

The pro-opiomelanocortin-derived peptide α-melanocyte stimulating hormone (α-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, β- and γ-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 μg lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO) level was seen in the animals' brains, when detected by electron paramagnetic resonance (EPR). All tested melanocortins, α-, β-, γ1- and γ2-MSH (0.001–10 nmol/mouse i.c.), dose dependently reduced the LPS induced increases in brain NO, with an order of effectiveness: β-MSH≥γ1-MSH=γ2-MSH>α-MSH. Our results suggest specialized functions of β- and γ-MSH melanocortins in inflammatory signal modulation in the brain.