کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2006759 | 1066352 | 2010 | 6 صفحه PDF | دانلود رایگان |
The anti-hypertensive peptide Arg-Ile-Tyr, which was isolated based on its inhibitory activity (IC50 = 28 μM) for angiotensin I-converting enzyme (ACE) from the subtilisin digest of rapeseed protein, exhibited vasorelaxing activity (EC50 = 5.1 μM) in an endothelium-dependent manner in the mesenteric artery of spontaneously hypertensive rats (SHRs). We named the peptide rapakinin. ACE inhibitors are reported to induce nitric oxide (NO)-dependent vasorelaxation by elevating the endogenous bradykinin level; however, the vasorelaxation induced by 10 μM of rapakinin was blocked only insignificantly by HOE140 or NG-nitro-l-arginine methyl ester (l-NAME), antagonists of bradykinin B2 receptor and an inhibitor of NO synthase, respectively. On the other hand, the vasorelaxation induced by 10 μM rapakinin was significantly blocked by indomethacin and CAY10441, a cyclooxygenase (COX) inhibitor and an antagonist of the IP receptor, respectively. The vasorelaxing activity of rapakinin was also blocked by lorglumide, an antagonist of the cholecystokinin (CCK) CCK1 receptor, although rapakinin has no affinity for the IP and CCK1 receptors. The vasorelaxation induced by 10 μM iloprost, an IP receptor agonist, was also blocked by lorglumide, suggesting that CCK–CCK1 receptor system is activated downstream of the PGI2–IP receptor system. The anti-hypertensive activity of rapakinin after oral administration in SHRs was also blocked by CAY10441 and lorglumide. These results suggest that the anti-hypertensive activity of rapakinin might be mediated mainly by the PGI2–IP receptor, followed by CCK–CCK1 receptor-dependent vasorelaxation.
Journal: Peptides - Volume 31, Issue 5, May 2010, Pages 909–914