Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on ma...

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Main Authors: Jie Ma, Yu Luo, Lilin Ge, Lei Wang, Mei Zhou, Yingqi Zhang, Jinao Duan, Tianbao Chen, Chris Shaw
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2014/564839
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author Jie Ma
Yu Luo
Lilin Ge
Lei Wang
Mei Zhou
Yingqi Zhang
Jinao Duan
Tianbao Chen
Chris Shaw
author_facet Jie Ma
Yu Luo
Lilin Ge
Lei Wang
Mei Zhou
Yingqi Zhang
Jinao Duan
Tianbao Chen
Chris Shaw
author_sort Jie Ma
collection DOAJ
description The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10−6 M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10−11 M and 10−5 M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140) and B2-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.
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institution Kabale University
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publishDate 2014-01-01
publisher Wiley
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series The Scientific World Journal
spelling doaj-art-595da85a8dcf4921be0d51370e9955392025-02-03T01:33:22ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/564839564839Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid FrogsJie Ma0Yu Luo1Lilin Ge2Lei Wang3Mei Zhou4Yingqi Zhang5Jinao Duan6Tianbao Chen7Chris Shaw8Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKThe First Hospital of Hebei Medical University, Shijiazhuang 050031, ChinaJiangsu Key Laboratory for Traditional Chinese Medicine (TCM) Formulae Research, Nanjing University of Chinese Medicine, Nanjing, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UKThe defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10−6 M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10−11 M and 10−5 M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140) and B2-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.http://dx.doi.org/10.1155/2014/564839
spellingShingle Jie Ma
Yu Luo
Lilin Ge
Lei Wang
Mei Zhou
Yingqi Zhang
Jinao Duan
Tianbao Chen
Chris Shaw
Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
The Scientific World Journal
title Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
title_full Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
title_fullStr Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
title_full_unstemmed Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
title_short Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs
title_sort ranakinestatin ppf from the skin secretion of the fukien gold striped pond frog pelophylax plancyi fukienensis a prototype of a novel class of bradykinin b2 receptor antagonist peptide from ranid frogs
url http://dx.doi.org/10.1155/2014/564839
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