The smooth muscle pharmacology of maximakinin, a receptor-selective, bradykinin-related nonadecapeptide from the venom of the Chinese toad, Bombina maxima.
Structural homologues of vertebrate regulatory peptides found in defensive skin secretions of anuran amphibians often display enhanced bioactivity and receptor binding when compared with endogenous mammalian peptide ligands. Maximakinin, a novel N-terminally extended bradykinin (DLPKINRKGPRPPGFSPFR) from the skin venom of a Chinese toad (Bombina maxima), displays such activity enhancement when compared with bradykinin but is additionally highly selective for mammalian arterial smooth muscle bradykinin receptors displaying a 50-fold increase in molar potency in this smooth muscle type. In contrast, a 100-fold decrease in molar potency was observed at bradykinin receptors in intestinal and uterine smooth muscle preparations. Maximakinin has thus evolved as a "smart" defensive weapon in the toad with receptor/tissue selective targeting. Natural selection of amphibian skin venom peptides for antipredator defence, through inter-species delivery by an exogenous secretory mode, produces subtle structural stabilisation modifications that can potentially provide new insights for the design of selectively targeted peptide therapeutics.
O'Rourke
Martin
M
School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
Chen
Tianbao
T
Hirst
David G
DG
Rao
Pingfan
P
Shaw
Chris
C
D000595:Amino Acid Sequence; D000664:Amphibian Venoms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D001158:Arteries / Q000187:drug effects*; D001681:Biological Assay; D001920:Bradykinin / Q000737:chemistry*; D065168:Bradykinin Receptor Antagonists; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D018002:Receptors, Bradykinin / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014688:Venoms / Q000737:chemistry*
D000664:Amphibian Venoms; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; D014688:Venoms; C497892:maximakinin, Bombina maxima; D001920:Bradykinin