Structure-activity studies of bradykinin analogues on rat mast cell histamine release.

Bradykinin (BK), kallidin (KD), and various analogues induced histamine release from rat mast cells. The results obtained with substituted analogues of BK indicated that: 1) the presence of both Arg residues at position 1 and 9 of kinins was favorable to confer histamine-releasing activity, 2) acetylation of the N-terminal amino acid residue led to a drastic reduction of this activity, 3) addition of a D-Arg residue at the N-terminus reduced their activity, as well as trans-4-hydroxyproline (Hyp) substitutions at position 2 or 3,4) D-Arg0 addition and Hyp3 substitution were synergistic in lowering activity, and 5) D-Phe7 substitution led to enhanced histamine-releasing activity.