Satoshi Yodonawa

Inhibition by a novel peptide leukotriene receptor antagonist ONO‐1078 of airway wall thickening and airway hyperresponsiveness to histamine induced by leukotriene C4 or leukotriene D4 in guinea‐pigs

We studied the effect of intravenous administration of leukotriene (LT) C4 or LTD., on airway responsiveness to histamine and airway wall thickening in guinea‐pigs. Guinea‐pigs were killed and the lungs were fixed in formalin. Slides from paraffin‐embedded section of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer, Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline‐Raw and peak‐Raw following intravenous administration of histamine before and after the intravenous administration of LTC4 or LTD4. The infusion of LTC4 or LTD4 induced an increase of the relative thickness of the airway wall in peripheral bronchi demonstrable by the histological examination. In analysis of airway function, intravenous administration of LTC4 or LTD4 induced airway hyperresponsiveness to histamine with airway wall thickening. The LTC4 and LTD4 receptor antagonist ONO‐1078 inhibited these effects of LTC4 and LTD4, suggesting LTC4 and LTD4 may induce airway wall thickening and airway hyperresponsiveness through LTC4 and LTD4 receptors in the airways.

Inhibition of 9α,11β-prostaglandin F2-induced bronchial hyperresponsiveness by thromboxane A2 receptor antagonists in guinea pigs

Abstract We studied the effect of intravenous administration of 9α, 11β-prostaglandin F 2 on bronchial responsiveness to histamine and airway wall thickening in guinea-pigs. The infusion of 9α, 11β-prostaglandin F 2 induced an increased of the relative thickness of the airway wall in peripheral bronchi demonstrable by histological examination. Analysis of airway function showed that the infusion of 9α,11β-prostaglandin F 2 induced airway hyperresponsiveness to histamine with airway wall thickening. The thromboxane A 2 receptor antagonists, ONO-NT-126 (5(Z)-6-[1R,2R,3R,4S)-3-(n-4-bromobenzenesulfonyl-aminomethyl) bicyclo-[2.2.1]heptane-2-yl]hex-5- enoic acid) and ONO-8809 (n-decyl(Z)-6-[(1S,2S,3S,4S)-3-(4-bromobenzenesulfonylaminometyl)biclo[2.2.1]hept-2-yl]-5-hexenoate), inhibited these effects of 9α,11β-prostaglandin F 2 in a dose-dependent manner.

Inhibition of bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C4 by novel thromboxane A2 receptor antagonists ONO-NT-126 and ONO-8809 in guinea-pigs.

We studied the effect of intravenous administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea‐pigs. Guinea‐pigs were killed and the lungs were fixed in formalin. Slides from paraffin‐embedded sections of the lungs were stained and the airways that were cut in transverse sections were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two incides, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline‐Raw and peak‐Raw following intravenous administration of histamine before and after the intravenous administration of LTC4. Intravenous administration of 3 μg/kg LTC4 for 1 hr induced an increase of the relative thickness of the airway wall in peripheral bronchi by the histological examination. In analysis of airway function, intravenous administration of 3 μg/kg LTC4 for 1 hr induced airway hyperresponsiveness to histamine with airway wall thickening. Thromboxane A2 receptor antagonists ONO‐NT‐126 and ONO‐8809 inhibited the LTC4‐induced airway hyperresponsiveness to histamine in a dose‐dependent manner, but not the airway wall thickening induced by LTC4, suggesting that the effect of LTC4 on bronchial hyperresponsiveness is likely to be mediated through TXA2.

Inhibition by thromboxane antagonists of airway hyperresponsiveness to histamine induced by 13,14‐dihydro‐15‐keto‐PGF2α in guinea‐pigs

Summary. We studied the effect of intravenous administration of 13,14‐dihydro‐15‐keto‐prostaglandin (PG) F27alpha; on airway responsiveness to histamine and airway wall thickening in guinea‐pigs. Guinea‐pigs were killed and the lungs were fixed in formalin. Slides from paraffin‐embedded sections of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline‐Raw and peak‐Raw following intravenous administration of histamine before and after the intravenous administration of 13,14‐dihydro‐l5‐keto‐PGF2n. Intravenous administration of 10/μg/kg 13,14‐dihydro‐15‐keto‐PGF2α for 1 h did not induce an increase of the relative thickness of the airway wall by the histological examination. In analysis of airway function, intravenous administration of 10μg/kg 13,14‐dihydro‐15‐keto‐PGF2α for 1 h induced airway hyperresponsiveness to histamine without airway wall thickening. Thromboxane A2 (TXA2) receptor antagonists ONO‐NT‐126 and ONO‐8809 inhibited the 13,14‐dihydro‐15‐keto‐PGF2α‐induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14‐dihydro‐15‐keto‐PGF2α on bronchial hyperresponsiveness is likely to be mediated through TXA2.