Orally administered novokinin, an angiotensin AT2 receptor agonist, suppresses food intake via prostaglandin E2-dependent mechanism in mice

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), having affinity for the AT2 receptor, is a potent vasorelaxing and hypotensive peptide designed based on the structure of ovokinin(2-7), a bioactive peptide derived from ovalbumin. Here we show that intracerebroventricularly (i.c.v.) administered novokinin dose-dependently suppresses food intake at a dose of 30-100 nmol/mouse in fasted conscious mice. Orally administered novokinin (30-100 mg/kg) also suppressed food intake. Novokinin suppressed food intake in wild-type and AT1 receptor-knockout mice but not in AT2 receptor-knockout mice after i.c.v. or oral administration. Novokinin-induced anorexigenic activity after i.c.v. administration was blocked by indomethacin, a cyclooxygenase inhibitor, or ONO-AE3-208, an antagonist for EP4 receptor for PGE2. Taken together, novokinin may suppress food intake via activation of PGE2-EP4, downstream of the AT2 receptor.