Effects of protizinic acid on leukokinin generation and its physiological action

The effect of protizinic acid (PRT), a non-steroidal antiinflammatory drug, on the in vivo leukokinin (LK) generation system using feline acute ischemia model, in vitro LK generation system and the LK-induced contraction of the isolated smooth muscle was investigated. When 3 mg/kg PRT was injected twice intravenously to cats with acute cardiac ischemia, increased blood acid protease activity was inhibited and significant inhibitory action on the decrease of leukokininogen, the precursor of LK, was observed. Simultaneously, ST-segment elevation on the electrocardiogram tended to be suppressed and the lowered mean aortic blood pressure was significantly restored. On the LK generation induced by rabbit kininogen and acid protease derived from mouse L-1210 leukemic cells or rabbit polymorphonuclear leukocytes, PRT showed a dose-dependent inhibition while indomethacin (IM) and ibuprofen (IB) at a concentration of 3 X 10(-4) M showed no effect. However, potencies of the inhibitory actions of PRT, IM and IB on the LK generation induced by bovine spleen Cathepsin D were almost the same at a concentration of 3 X 10(-4) M. Furthermore, PRT as well as IM showed antagonistic action on the isolated rat uterine contraction induced by LK. These results suggest that PRT not only inhibits the in vitro and in vivo generation of LK but also antagonizes to it on the receptor site of LK.