title: A novel bradykinin-related dodecapeptide (RVALPPGFTPLR) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis) exhibiting unusual structural and functional features.
abstract: Bradykinin-related peptides (BRPs) are significant components of the defensive skin secretions of many anuran amphibians, and these secretions represent the source of the most diverse spectrum of such peptides so far encountered in nature. Of the many families of bioactive peptides that have been identified from this source, the BRPs uniquely appear to represent homologues of counterparts that have specific distributions and receptor targets within discrete vertebrate taxa, ranging from fishes through mammals. Their broad spectra of actions, including pain and inflammation induction and smooth muscle effects, make these peptides ideal weapons in predator deterrence. Here, we describe a novel 12-mer BRP (RVALPPGFTPLR-RVAL-(L¹, T⁶, L⁸)-bradykinin) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis). The C-terminal 9 residues of this BRP (-LPPGFTPLR) exhibit three amino acid substitutions (L/R at Position 1, T/S at Position 6 and L/F at Position 8) when compared to canonical mammalian bradykinin (BK), but are identical to the kinin sequence present within the cloned kininogen-2 from the Chinese soft-shelled turtle (Pelodiscus sinensis) and differ from that encoded by kininogen-2 of the Tibetan ground tit (Pseudopodoces humilis) at just a single site (F/L at Position 8). These data would imply that the novel BRP is an amphibian defensive agent against predation by sympatric turtles and also that the primary structure of the avian BK, ornithokinin (RPPGFTPLR), is not invariant within this taxon. Synthetic RVAL-(L¹, T⁶, L⁸)-bradykinin was found to be an antagonist of BK-induced rat tail artery smooth muscle relaxation acting via the B2-receptor.
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. dshi01@qub.ac.uk.
authors.forename: Daning
authors.initials: D
authors.lastname: Shi
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. yluo03@qub.ac.uk.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. qdu01@qub.ac.uk.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. l.wang@qub.ac.uk.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. m.zhou@qub.ac.uk.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. jma04@qub.ac.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, Northern Ireland, UK. r.li@qub.ac.uk.
authors.forename: Renjie
authors.initials: R
authors.lastname: Li
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. t.chen@qub.ac.uk.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. chris.shaw@qub.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000378:metabolism*; D001483:Base Sequence; D001920:Bradykinin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular; D019295:Computational Biology; D015723:Gene Library; D007704:Kininogens / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
chemical_list: D007704:Kininogens; D043782:Receptor, Bradykinin B2; C062138:ornitho-kinin; D001920:Bradykinin