title: Hypotensive activity of novokinin, a potent analogue of ovokinin(2-7), is mediated by angiotensin AT(2) receptor and prostaglandin IP receptor.
abstract: Novokinin (Arg-Pro-Leu-Lys-Pro-Trp) is a potent hypotensive peptide previously designed based on the structure of ovokinin(2-7) (Arg-Ala-Asp-His-Pro-Phe), a vasorelaxing and hypotensive peptide derived from ovalbumin. Novokinin exhibited an affinity for the angiotensin AT(2) receptor (Ki=7.35 microM). Novokinin significantly lowered systolic blood pressure at a dose of 0.03 and 0.1 mg/kg after intravenous and oral administration, respectively, in spontaneously hypertensive rats (SHRs), and the hypotensive activity was blocked by PD123319, an antagonist of the AT(2) receptor. Novokinin lowered blood pressure in C57BL/6J mice after oral administration at a dose of 50 mg/kg. However, in AT(2) receptor-deficient mice, novokinin did not reduce blood pressure. These results demonstrate that the hypotensive activity of novokinin is mediated by the AT(2) receptor. The hypotensive activity of novokinin in SHRs was completely blocked by indomethacin and CAY10441, an inhibitor of cyclooxygenase and an antagonist of the prostaglandin IP receptor, respectively. These suggest that the hypotensive activity is mediated by prostacyclin and the IP receptor downstream of the AT(2) receptor.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan. yyamada@kais.kyoto-u.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Daiki
authors.initials: D
authors.lastname: Yamauchi
authors.forename: Hachiro
authors.initials: H
authors.lastname: Usui
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Megumi
authors.initials: M
authors.lastname: Yokoo
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000284:Administration, Oral; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004527:Egg Proteins / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; C511871:Arg-Pro-Leu-Lys-Pro-Trp; D004527:Egg Proteins; D007093:Imidazoles; D009842:Oligopeptides; D010446:Peptide Fragments; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011982:Receptors, Prostaglandin; C096585:ovokinin; C073402:PD 123319