Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain.
The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 microg 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, alpha-, beta-, gamma1- and gamma2-MSH (0.001-10 nmol/mouse i.c.), dose dependently reduced the LPS induced increases in brain NO, with an order of effectiveness: beta-MSH > or = gamma1-MSH=gamma2-MSH>alpha-MSH. Our results suggest specialized functions of beta- and gamma-MSH melanocortins in inflammatory signal modulation in the brain.
Muceniece
Ruta
R
Department of Pharmacy, Faculty of Medicine, University of Latvia, Sarlotes iela la, 1001 Riga, Latvia. rutam@latnet.lv
Zvejniece
Liga
L
Kirjanova
Olga
O
Liepinsh
Edgars
E
Krigere
Liga
L
Baumane
Larisa
L
Kalvinsh
Ivars
I
Wikberg
Jarl E S
JE
Dambrova
Maija
M
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology; D019824:beta-MSH / Q000378:metabolism* / Q000494:pharmacology; D019825:gamma-MSH / Q000378:metabolism* / Q000494:pharmacology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019824:beta-MSH; D019825:gamma-MSH; D009569:Nitric Oxide; D000521:alpha-MSH