Orally administered novokinin, an angiotensin AT sub(2) receptor agonist, suppresses food intake via prostaglandin E sub(2)-dependent mechanism in mice

• Published in: Peptides (New York, N.Y. : 1980) Vol. 30; no. 6; pp. 1105 - 1108
• Main Authors: Ohinata, Kousaku, Fujiwata, Yoko, Shingo, Fukumoto, Masaru, Iwai, Masatsugu, Horiuchi, Yoshikawa, Masaaki
• Format: Journal Article
• Language: English
• Published: 01-06-2009
• ISSN: 0196-9781
• DOI: 10.1016/j.peptides.2009.03.003

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), having affinity for the AT sub(2) 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 AT sub(1) receptor-knockout mice but not in AT sub(2) 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 EP sub(4) receptor for PGE sub(2). Taken together, novokinin may suppress food intake via activation of PGE sub(2)-EP sub(4), downstream of the AT sub(2) receptor.