On the role of basic residues of head-to-tail cyclic bradykinin analogues on rat duodenum relaxation

Three linear bradykinin (BK) analogues, Lys-Lys-BK, Nle-Lys-BK and Lys-Nle-BK and their head-to-tail cyclic analogues, along with cyclo-Nle-Nle-BK and cyclo-Lys-Lys-[Trp5]BK, were synthesized and tested on an isolated rat duodenum preparation. All kinins, except the [Trp5]-analogue, cause relaxation with EC50values in the picomolar range. The most potent linear analogue (Lys-Nle-BK) is about 40 times more active than BK and the most potent cyclic kinin (cyclo-Nle-Lys-BK) is about 6 times more active. Present results suggest that the significant potency of cyclo-Lys-Lys-BK, the earlier most potent cyclic kinin which is only a little less potent than linear BK, depends on the ring size rather than on the presence of the extra basic residues.