Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions.
Bradykinin-related peptides (BRPs) are one of the most extensively studied frog secretions-derived peptide families identified from many amphibian species. The diverse primary structures of BRPs have been proven essential for providing valuable information in understanding basic mechanisms associated with drug modification. Here, we isolated, identified and characterized a dodeca-BRP (RAP-L1, T6-BK), with primary structure RAPLPPGFTPFR, from the skin secretions of Chinese large odorous frogs,Odorrana livida. This novel peptide exhibited a dose-dependent contractile property on rat bladder and rat ileum, and increased the contraction frequency on rat uterus ex vivo smooth muscle preparations; it also showed vasorelaxant activity on rat tail artery smooth muscle. In addition, the analogue RAP-L1, T6, L8-BK completely abolished these effects on selected rat smooth muscle tissues, whilst it showed inhibition effect on bradykinin-induced rat tail artery relaxation. By using canonical antagonist for bradykinin B1 or B2 type receptors, we found that RAP-L1, T6-BK -induced relaxation of the arterial smooth muscle was very likely to be modulated by B2 receptors. The analogue RAP-L1, T6, L8-BK further enhanced the bradykinin inhibitory activity only under the condition of co-administration with HOE140 on rat tail artery, suggesting a synergistic inhibition mechanism by which targeting B2 type receptors.
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. jxiang01@qub.ac.uk.
Jie
J
Xiang
School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, China. wanghuiheidi@126.com.
Hui
H
Wang
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. c.ma@qub.ac.uk.
Chengbang
C
Ma
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. m.zhou@qub.ac.uk.
Mei
M
Zhou
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. yuxin.wu@qub.ac.uk.
Yuxin
Y
Wu
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. l.wang@qub.ac.uk.
Lei
L
Wang
Department of Nutrition and Food Science, College of Agriculture and Life Sciences, Texas A&M University, 123A Cater Mattil Hall, 2253 TAMU, College Station, TX 77843, USA. shaodong.guo@tamu.edu.
Shaodong
S
Guo
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. t.chen@qub.ac.uk.
Tianbao
T
Chen
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK. chris.shaw@qub.ac.uk.
Chris
C
Shaw
B2 receptor; agonist and antagonist; bradykinin related peptide (BRP); rat tail artery; smooth muscle
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