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Inhibition by a novel peptide leukotriene receptor antagonist ONO‐1078 of airway wall thickening and airway hyperresponsiveness to histamine induced by leukotriene C 4 or leukotriene D 4 in guinea‐pigs
Author(s) -
KUROSAWA M.,
YODONAWA S.,
TSUKAGOSHI H.,
MIYACHI Y.
Publication year - 1994
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.1994.tb02729.x
Subject(s) - histamine , leukotriene , leukotriene d4 , medicine , airway , leukotriene receptor , airway resistance , guinea pig , leukotriene c4 , antagonist , anesthesia , immunology , pharmacology , receptor , asthma
Summary We studied the effect of intravenous administration of leukotriene (LT) C 4 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 LTC 4 or LTD 4 . The infusion of LTC 4 or LTD 4 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 LTC 4 or LTD 4 induced airway hyperresponsiveness to histamine with airway wall thickening. The LTC 4 and LTD 4 receptor antagonist ONO‐1078 inhibited these effects of LTC 4 and LTD 4 , suggesting LTC 4 and LTD 4 may induce airway wall thickening and airway hyperresponsiveness through LTC 4 and LTD 4 receptors in the airways.