Effect of a new leukotriene receptor antagonist, ONO-1078, on human bronchial smooth muscle in vitro
| Autor: | Kazuto Hirata, Haruhiko Matsushita, Hiroshi Kanazawa, Tadanao Takeda, Naotsugu Kurihara, Hiroshi Fujiwara, Ohta |
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| Rok vydání: | 1993 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Bronchoconstriction Clinical Biochemistry Bronchi Endogeny Peptide In Vitro Techniques Basal (phylogenetics) Internal medicine medicine Animals Humans Receptors Immunologic Aged Receptors Leukotriene chemistry.chemical_classification Mites Leukotriene receptor business.industry Diphenhydramine Antagonist Muscle Smooth Cell Biology Allergens Receptor antagonist In vitro Endocrinology chemistry Chromones Female SRS-A business Muscle Contraction medicine.drug |
| Zdroj: | Prostaglandins, Leukotrienes and Essential Fatty Acids. 48:241-246 |
| ISSN: | 0952-3278 |
| Popis: | 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°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 LTC 4 or LTD 4 (3 × 10 −8 M). Pretreatment of bronchi with ONO-1078 (10 −8 M, 10 −7 M) significantly inhibited dose-dependent contractions induced by LTC 4 and LTD 4 . 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 H 1 -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. |
| Databáze: | OpenAIRE |
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