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 associate...
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MDPI AG
2016-09-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/10/283 |
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| author | Jie Xiang Hui Wang Chengbang Ma Mei Zhou Yuxin Wu Lei Wang Shaodong Guo Tianbao Chen Chris Shaw |
| author_facet | Jie Xiang Hui Wang Chengbang Ma Mei Zhou Yuxin Wu Lei Wang Shaodong Guo Tianbao Chen Chris Shaw |
| author_sort | Jie Xiang |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-04-11T18:27:01Z |
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| spelling | doaj.art-ed7ae7d71a894f0daaae5fe9941753d82022-12-22T04:09:36ZengMDPI AGToxins2072-66512016-09-0181028310.3390/toxins8100283toxins8100283Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin SecretionsJie Xiang0Hui Wang1Chengbang Ma2Mei Zhou3Yuxin Wu4Lei Wang5Shaodong Guo6Tianbao Chen7Chris Shaw8Natural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKSchool of Pharmaceutical Sciences, China Medical University, Shenyang 110001, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKDepartment 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, USANatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKBradykinin-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.http://www.mdpi.com/2072-6651/8/10/283bradykinin related peptide (BRP)B2 receptorrat tail arteryagonist and antagonistsmooth muscle |
| spellingShingle | Jie Xiang Hui Wang Chengbang Ma Mei Zhou Yuxin Wu Lei Wang Shaodong Guo Tianbao Chen Chris Shaw Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions Toxins bradykinin related peptide (BRP) B2 receptor rat tail artery agonist and antagonist smooth muscle |
| title | Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions |
| title_full | Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions |
| title_fullStr | Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions |
| title_full_unstemmed | Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions |
| title_short | Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions |
| title_sort | ex vivo smooth muscle pharmacological effects of a novel bradykinin related peptide and its analogue from chinese large odorous frog odorrana livida skin secretions |
| topic | bradykinin related peptide (BRP) B2 receptor rat tail artery agonist and antagonist smooth muscle |
| url | http://www.mdpi.com/2072-6651/8/10/283 |
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