Peptide DV-28 amide: An inhibitor of bradykinin-induced arterial smooth muscle relaxation encoded by Bombina orientalis skin kininogen-2.
Skin kininogens from bombinid toads encode an array of bradykinin-related peptides and one such kininogen from Bombina maxima also encodes the potent bradykinin B2-receptor antagonist, kinestatin. In order to determine if the skin secretion of the closely-related toad, Bombina orientalis, contained a bradykinin inhibitory peptide related to kinestatin, we screened reverse phase HPLC fractions of defensive skin secretion using a rat tail artery smooth muscle preparation. A fraction was located that inhibited bradykinin-induced relaxation of the preparation and this contained a peptide of 3198.5Da as determined by MALDI-TOF MS. Automated Edman degradation of this peptide established the identity of a 28-mer as: DMYEIKGFKSAHGRPRVCPPGEQCPIWV, with a disulfide-bridge between Cys(18) and Cys(24) and an amidated C-terminal Val residue. Peptide DV-28 was found to correspond to residues 133-160 of skin pre-kininogen-2 of B. orientalis that also encodes two copies of (Thr(6))-bradykinin. The C-terminal residue, Gly-161, of the precursor open-reading frame, acts as the C-terminal amide donor of mature DV-28. DV-28 amide thus represents a new class of bradykinin inhibitor peptide from amphibian skin secretion.
Molecular Therapeutics Research, School of Pharmacy, Queen's University, Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
Lei
L
Wang
Yong
Y
Chen
Mu
M
Yang
Mei
M
Zhou
Tianbao
T
Chen
Da-Yuan
DY
Sui
Chris
C
Shaw
D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D007704:Kininogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism*
D065094:Bradykinin B2 Receptor Antagonists; D007704:Kininogens; D010455:Peptides; D001920:Bradykinin