STRUCTURE-ACTIVITY STUDIES OF BRADYKININ ANALOGS 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.