Takeshi Ishizaki

Inhibitory effect of N-(3',4'-dimethoxycinnamoyl)anthranilic acid(N-5') on SRS-A mediated bronchoconstriction in the guinea pig in vivo

Slow‐reacting substance of anaphylaxis (SRS‐A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS‐A‐mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of N‐(3′, 4′‐dimethoxycinnamoyl) anthranilic acid (N‐5′), a new anti‐allergic drug, on the bronchoconstriction. FPL 55712 inhibited most of the bronchoconstriction induced by antigen inhalation. N‐5′inhibited the antigen‐induced bronchoconstriction in a dose‐dependent fashion. Intraperitoneal administration of 200 mg/kg N‐5′was effective for 40 min after antigen inhalation, while the effect of 60 mg/kg lasted only 7 min. On the other hand, 200 mg/kg N‐5′showed no inhibitory effect on the bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS‐A. These findings indicate that one of the anti‐allergic actions of N‐5′is due to inhibition of synthesis and/or release of SRS‐A.

Effects of Ca2+ Antagonist, Nicardipine, on Experimental Asthma With Special Reference to Slow Reacting Substance of Anaphylaxis

Slow reacting substance of anaphylaxis (SRS‐A) is an important chemical mediator of bronchial asthma. Leukotriene C4 is a component of SRS‐A and is synthesized from arachidonic acid. Its synthesizing and releasing processes are found to he Ca2+‐dependent. We developed an in vivo inhalation asthma model, mainly mediated by SRS‐A, and elucidated the relationship between a Ca2+‐antagonist, nicardipine, and SRS‐A. In the asthmatic model, mediated by endogenous SRS‐A induced by antigen inhalation, continuous intravenous infusion of nicardipine 7 μg/kg/min depressed the open airway pressure by about 60% compared with the saline‐treated group. Inhibition of mean pulmonary resistance (RL) was about 50% and that of the inverted value of dynamic compliance (1/Cdyn) about 36%. However, the same concentration of nicardipine did not significantly affect the airway response in the asthmatic model induced by the inhalation of leukotriene C4. These results suggest that nicardipine, at the concentration used in the present study, did not block the direct effect of SRS‐A on the smooth muscle, but blocked the Ca2+ influx required for the synthesis of SRS‐A and its release.