Bradykinin (BK) and bradykinin-related peptides (BRPs), which were identified from\na diversity of amphibian skin secretions, exerted contractile and relaxing effects on non-vascular\nand vascular smooth muscle, respectively. Here, we report a novel bradykinin-related peptide\nwith a molecular mass of 1890.2 Da, RVAGPDKPARISGLSPLR, which was isolated and identified\nfrom Ordorrana hejiangensis skin secretions, followed by a C-terminal extension sequence VAPQIV.\nThe biosynthetic precursor-encoding cDNA was cloned by the â??shotgunâ? cloning method, and the\nnovel RR-18 was identified and structurally confirmed by high-performance liquid chromatography\n(HPLC) and tandem mass spectrometry (MS/MS). Subsequently, the myotropic activity of the\nsynthetic replicate of RR-18 was investigated on the rat bladder, uterus, tail artery and ileum\nsmooth muscle. The peptide was named RR-18 in accordance (R = N-terminal arginine,\nR = C-terminal arginine, 18 = number of residues). In this study, the synthetic replicates of RR-18\nshowed no agonist/antagonism of BK-induced rat bladder and uterus smooth muscle contraction.\nHowever, it displayed an antagonism of bradykinin-induced rat ileum contraction and arterial\nsmooth muscle relaxation. The EC50 values of BK for ileum and artery, were 214.7 nM and 18.3 nM,\nrespectively. When the tissue was pretreated with the novel peptide, RR-18, at the maximally effective\nconcentration of bradykinin (1 x 10-6 M), bradykinin-induced contraction of the ileum and relaxation\nof the arterial smooth muscle was reduced by 50â??60% and 30â??40%, respectively. In conclusion, RR-18\nrepresents novel bradykinin antagonising peptide from amphibian skin secretions. It may provide\nnew insight into possible treatment options for chronic pain and chronic inflammation.
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