Complement C5a stimulates food intake via a prostaglandin D(2)- and neuropeptide Y-dependent mechanism in mice.
We have recently found that prostaglandin (PG) D(2) stimulates food intake via DP(1) 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 DP(1) 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)-DP(1) 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)-DP(1) 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.
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan. ohinata@kais.kyoto-u.ac.jp
Kousaku
K
Ohinata
Kuniko
K
Takagi
Kyoko
K
Biyajima
Kentaro
K
Kaneko
Chihiro
C
Miyamoto
Akihiro
A
Asakawa
Naomi
N
Eguchi
Yoshihiro
Y
Urade
Akio
A
Inui
Masaaki
M
Yoshikawa
D000818:Animals; D015936:Complement C5a / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D006827:Hydantoins / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000502:physiology*; D015230:Prostaglandin D2 / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006827:Hydantoins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C527097:prostanoid D receptor 1, mouse; C058848:BW A868C; D015936:Complement C5a; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015230:Prostaglandin D2