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.
abstract: 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.
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Yu
authors.identifier: 0000-0002-5095-5206
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ge
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Lei
authors.identifier: 0000-0002-8811-8489
authors.initials: L
authors.lastname: Wang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Mei
authors.identifier: 0000-0003-2576-0252
authors.initials: M
authors.lastname: Zhou
authors.affiliation: The First Hospital of Hebei Medical University, Shijiazhuang 050031, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Traditional Chinese Medicine (TCM) Formulae Research, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Tianbao
authors.identifier: 0000-0001-8011-9260
authors.initials: T
authors.lastname: Chen
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists / Q000378:metabolism* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology*; D011898:Ranidae / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000378:metabolism*
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D010455:Peptides