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 values for linear bradykinin analogues. Cyclic Lys-bradykinin reversibly antagonized the transmission from the cereal nerve fibres to the nicotinic receptor 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 caused 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 action of linear bradykinin analogues in both mammalian smooth muscle (i.e. duodenum) and insect CNS. This is the first successful step in the developing of a stable equi-active bradykinin analogue.