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

Peptides
Yuko YamadaMasaaki Yoshikawa

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.

References

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Citations

Feb 15, 2014·BioMed Research International·Subhadeep ChakrabartiJianping Wu
Aug 26, 2014·Pharmacological Reports : PR·Bożena BądzyńskaElżbieta Kompanowska-Jezierska
Jan 16, 2013·International Journal of Hypertension·Marie-Odile Guimond, Nicole Gallo-Payet
Sep 10, 2010·The Journal of Investigative Dermatology·Stéphanie GohinBérengère Fromy
Apr 3, 2021·Molecular Pharmacology·Arina RanjitAli Aghazadeh-Habashi

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