title: The smooth muscle pharmacology of maximakinin, a receptor-selective, bradykinin-related nonadecapeptide from the venom of the Chinese toad, Bombina maxima.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: O'Rourke
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: David G
authors.initials: DG
authors.lastname: Hirst
authors.forename: Pingfan
authors.initials: P
authors.lastname: Rao
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: 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*
chemical_list: D000664:Amphibian Venoms; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; D014688:Venoms; C497892:maximakinin, Bombina maxima; D001920:Bradykinin