Pharmacological activities of cyclic bradykinin analogues

Cyclic bradykinin, cyclic Lys-bradykinin and cyclic Lys-Lys-bradykinin were examined, using the isolated preparation of the rat duodenum and the giant interneuron in the terminal abdominal ganglion of the cockroach. Cyclo-Lys -Lys-bradykinin caused a relaxation of the rat duodenum with an EC50-value of 4.2 (+/- 0.8)x10(-10) M (+/- SEM, n=4), which is comparable to the value s for linear bradykinin analogues. Cyclic Lys-bradykinin reversibly antagon ized the transmission from the cereal nerve fibres to the nicotinic recepto r on the giant interneuron with an EC50-value of 4.5 (+/- 0.5) x 10(-6) M ( +/- SEM, n=4), which is about one order of the magnitude lower than that ca used by cyclic Lys-Lys-bradykinin with an EC50 of 3.1 (+/- 0.3) x 10(-5) M (+/- SEM, n=5) and cyclic bradykinin with an EC50 of 2.9 (+/- 0.2) x 10(-5) M (+/- SEM, n=4), and much lower than the EC50 values for linear analogues (> 10(-4) M). It is concluded that cyclic bradykinin analogues mimic the a ction of linear bradykinin analogues in both mammalian smooth muscle (i.e. duodenum) and insect CNS. This is the first successful step in the developi ng of a stable equi-active bradykinin analogue.