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薬理と治療
Abstract
Exposure of sensitized animals to antigens brings immediate asthmatic response characterized by β2-stimulant-sensitive bronchoconstriction and late asthmatic response characterized by β2-stimulant-resistant persistent airway inflammation. To examine implication of cysteinyl leukotriene 2(CysLT2)receptors in late asthmatic response, we evaluated effects of cysteinyl leukotriene 1(CysLT1) receptor antagonist(montelukast)and CysLT1 and CysLT2 receptor dual antagonist (ONO-6950)on late phase airway resistance and pulmonary eosinophil infiltration followed by ovalbumin(OVA)challenge in actively sensitized guinea pigs. The experiments were performed with or without the treatment of S-hexyl GSH, because S-hexyl GSH can elicit CysLT2 receptor dependent airway responses in guinea pigs as we have previously reported. In non-S-hexyl GSH treated guinea pigs, ONO-6950(3 mg╱kg, p. o.)and montelukast(1 mg╱kg, p. o.)equally attenuated OVA-induced increase in late phase airway resistance. On the other hand, in S-hexyl GSH-treated guinea pigs only ONO-6950, but not montelukast, significantly inhibited OVA-induced increase in late phase airway resistance. Number of eosinophils recovered from bronchoalveolar lavage fluid 22-24 hours after OVA challenge was equally reduced by montelukast and ONO-6950 regardless of S-hexyl GSH treatment. This result suggests that CysLT2 receptors as well as CysLT1 receptors play an important role in the development of late phase airway resistance. Therefore, ONO-6950, orally active dual CysLT1╱LT2 receptor antagonist, is expected to improve airway inflammation more potently than montelukast, CysLT1 receptor antagonist.
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