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

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.