Hypotensive activity of novokinin, a potent analogue of ovokinin(2–7), is mediated by angiotensin AT₂ receptor and prostaglandin IP receptor

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• 作者：Yuko Yamada ; Daiki Yamauchi ; Hachiro Usui ; Hui Zhao ; Megumi Yokoo ; Kousaku Ohinata ; Masaru Iwai ; Masatsugu Horiuchi ; Masaaki Yoshikawa
• 关键词：Novokinin ; Ovokinin(2– ; 7) ; Angiotensin ; AT₂ receptor ; Prostacyclin ; IP receptor ; Nitric oxide ; Blood pressure ; Spontaneously hypertensive rat
• 刊名：Peptides
• 出版年：2008
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：March 2008
• 卷：29
• 期：3
• 页码：412-418
• 文件大小：691 K

摘要

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 AT₂ receptor (Ki = 7.35 μM). 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 AT₂ receptor. Novokinin lowered blood pressure in C57BL/6J mice after oral administration at a dose of 50 mg/kg. However, in AT₂ receptor-deficient mice, novokinin did not reduce blood pressure. These results demonstrate that the hypotensive activity of novokinin is mediated by the AT₂ 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 AT₂ receptor.