Central action of bradykinin (I) Electroencephalogram of bradykinin and its degradation system in rat brain.

Both in vivo and in vitro experiments were performed to elucidate the relationship between the action of bradykinin (BK) and the possibility of release of pharmacologically active fragments from BK in the rat brain. In in vivo experiments, the activities of electroencephalogram (EEG) increased immediately after the intracerebral administration of 5 nmole BK. The effect was prolonged by intracerebral pretreatment of o-phenanthroline which inhibits plasma kininases. In vitro experiments, o-phenanthroline inhibited partially purified enzyme of rat brain which released fragments of BK possessing phenylalanine, serine, proline and/or arginine as N-terminal amino acids. Only arginine and minute amounts of phenylalanine were observed after the incubation with o-phenanthroline. The evidence suggests that the inhibition of the enzyme by o-phenanthroline resulted in a prolongation of the excited phase produced by BK on the EEG and on behavior. Supporting evidence indicates that Ser-Pro containing fragments derived from BK are concerned with the sedative phase of BK which was observed after the excitative stage.