Structure–activity studies of [des-Arg9]-bradykinin on the B1 receptor of the rabbit aorta

Abstract

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 angiotensin-iike effect when applied at very high concentrations.