Yamada Yuko, Yamauchi Daiki, Usui Hachiro, Zhao Hui, Yokoo Megumi, Ohinata Kousaku, Iwai Masaru, Horiuchi Masatsugu, Yoshikawa Masaaki
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Peptides. 2008 Mar;29(3):412-8. doi: 10.1016/j.peptides.2007.11.017. Epub 2007 Dec 4.
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.
新激肽（Arg-Pro-Leu-Lys-Pro-Trp）是一种强效降压肽，它之前是基于卵白蛋白衍生的血管舒张和降压肽卵激肽（2-7）（Arg-Ala-Asp-His-Pro-Phe）的结构设计而成。新激肽对血管紧张素AT(2)受体具有亲和力（Ki = 7.35 microM）。在自发性高血压大鼠（SHRs）中，新激肽分别经静脉和口服给药，剂量为0.03和0.1 mg/kg时，可显著降低收缩压，且其降压活性被AT(2)受体拮抗剂PD123319所阻断。新激肽以50 mg/kg的剂量口服给药后可降低C57BL/6J小鼠的血压。然而，在AT(2)受体缺陷型小鼠中，新激肽并未降低血压。这些结果表明，新激肽的降压活性是由AT(2)受体介导的。新激肽在SHRs中的降压活性分别被消炎痛和CAY10441完全阻断，CAY10441是一种环氧化酶抑制剂和前列腺素IP受体拮抗剂。这些结果提示，降压活性是由前列环素和AT(2)受体下游的IP受体介导的。
