Effect of a new leukotriene receptor antagonist, ONO-1078, on human bronchial smooth muscle in vitro.
Peptide leukotrienes (LT) have been postulated to play a major role in the etiology of bronchial asthma. The present study investigated the effect of a new peptide LT receptor antagonist, ONO-1078, on isolated human bronchial smooth muscle in vitro. Helical strips of bronchi were suspended in the organ baths filled with 37 degrees C Krebs solution and mechanical responses were recorded isometrically. ONO-1078 produced dose-dependent relaxations, which suggested that the spontaneous basal tone was in part mediated by LT. ONO-1078 caused dose-dependent relaxations of the tissues which were precontracted with LTC4 or LTD4 (3 x 10(-8) M). Pretreatment of bronchi with ONO-1078 (10(-8) M, 10(-7) M) significantly inhibited dose-dependent contractions induced by LTC4 and LTD4. ONO-1078 (10(-6) M) also significantly reduced the antigen-induced contractions in bronchi passively sensitized with atopic serum from mite-allergic patients. Moreover the combination of an H1-receptor antagonist, diphenhydramine (10(-5) M), and ONO-1078 (10(-6) M) completely abolished the antigen-induced contractions. The present findings demonstrate that ONO-1078 is a potent antagonist of exogenous and endogenous LT in the human airway. The selective LT antagonist such as ONO-1078 may be valuable in the therapy of allergic asthma.
First Department of Internal Medicine, Osaka City University Medical School, Japan.
H
H
Fujiwara
N
N
Kurihara
Ohta
K
K
Hirata
H
H
Matsushita
H
H
Kanazawa
T
T
Takeda
D000368:Aged; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008925:Mites / Q000276:immunology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D000485:Allergens; D002867:Chromones; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C047681:pranlukast