STRUCTURE-ACTIVITY STUDIES OF [DES-ARG-9]-BRADYKININ ON THE B1 RECEPTOR OF THE RABBIT AORTA

Eight L-alanine analogues of [des-Arg9]-bradykinin and a few other compounds substituted in positions 5 and (or) 8 have been tested on rabbit aortic strips in order to identify the group(s) responsible for binding and (or) stimulation of the B1 receptor. The results obtained with the L-Ala series have shown that the active group is located at the C-terminal end and it is probably Phe8, while the middle part and the N-terminal end of the peptide molecule are primarily involved in binding the agonist to the receptor. An aromatic ring is required in position 8 for activation of receptors, since the elimination of aromaticity (as in [Leu8, des-Arg9]-bradykinin and in [cyclohexylalanine8, des-Arg9]-bradykinin) brings about pure and competitive antagonists. Some compounds exert an agiotensin-like effect when applied at very high concentrations.