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.　(C)　2004　Elsevier　B.V.　All　rights　reserved.