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 AT(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 (30-100mg/kg) also suppressed food intake. Novokinin suppressed food intake in wild-type and AT(1) receptor-knockout mice but not in AT(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(4) receptor for PGE(2). Taken together, novokinin may suppress food intake via activation of PGE(2)-EP(4), downstream of the AT(2) receptor.
Ohinata
Kousaku
K
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan. ohinata@kais.kyoto-u.ac.jp
Fujiwata
Yoko
Y
Shingo
Fukumoto
F
Masaru
Iwai
I
Masatsugu
Horiuchi
H
Yoshikawa
Masaaki
M
D000818:Animals; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D010654:Phenylbutyrates / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D013997:Time Factors
C487890:4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid; C511871:Arg-Pro-Leu-Lys-Pro-Trp; D009281:Naphthalenes; D009842:Oligopeptides; D010654:Phenylbutyrates; D044139:Receptor, Angiotensin, Type 2; D015232:Dinoprostone; D007213:Indomethacin