Suppression of food intake by a complement C3a agonist [Trp5]-oryzatensin(5–9)

Abstract: [Trp5]-oryzatensin(5–9) (WPLPR), an agonist peptide for complement C3a receptor, has been designed based on the C-terminal region of ileum-contracting peptide oryzatensin derived from rice protein. We previously reported that WPLPR has anti-analgesic and anti-amnesic activities after central or oral administration. In this study, we found a novel function of WPLPR on food intake. WPLPR suppressed food intake after intracerebroventricular or intraperitoneal (i.p.) administration at a dose of 3–30nmol/mouse or 30–300mg/kg, respectively, in fasted mice. Orally administered WPLPR at a dose of 300mg/kg also decreased food intake. WPLPR decreased gastric emptying after i.p. injection at a dose of 300mg/kg. The anorexigenic activity of WPLPR was blocked by cyclooxygenase inhibitor or antagonist for prostaglandin (PG) E receptor EP4 subtype. These results suggest that WPLPR decreases food intake through PGE2 production followed by EP4 receptor activation. [Copyright &y& Elsevier]