Complement C5a stimulates food intake via a prostaglandin D2- and neuropeptide Y-dependent mechanism in mice

We have recently found that prostaglandin (PG) D-2 stimulates food intake via DP1 receptor. Here we show that complement C5a stimulates food intake by activating the orexigenic PGD(2) system. C5a (30-100 pmol/mouse), after intracerebroventricular administration, stimulated food intake in non-food-deprived mice. The orexigenic activity of C5a was blocked by co-administration of a DP1 receptor antagonist, BWA868C. Central administration of C5a elevated the hypothalamic mRNA expression of COX-2 but not COX-1, and the food intake stimulation of C5a was inhibited by pretreatment with a COX-2 inhibitor, celecoxib, suggesting that C5a activates COX-2 upstream of the PGD(2)-DP1 system. The orexigenic activity of C5a was also inhibited by an antagonist for neuropeptide Y (NPY) Y-1 receptor, which was activated downstream of the PGD(2)-DP1 system. These results suggest that C5a stimulates food intake via a PGD(2)- and NPY-dependent mechanism. C5a is the first example of orexigenic peptides acting through the PGD(2)-NPY system in the central nervous system. (C) 2009 Elsevier Inc. All rights reserved.