Effects of MKS-492 on Antigen-Induced Bronchoconstriction and Allergic Reaction in Guinea Pigs and Rats.
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概要
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Effects of R[+]-8-{[1-[3, 4-dimethoxyphenyl]-2-hydroxyethyl]amino}-3, 7-dihydro-7-[2-methoxyethyl]-1, 3-dimethyl-1<I>H</I>-purine-2, 6-dione (MKS-492), a reported type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen or platelet activating factor (PAF)-induced bronchoconstriction and allergic reactions in guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2) MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in airway responsiveness to histamine in guinea pigs, although aminophylline failed to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle invitro more potently than aminophylline. 4) MKS-492 inhibited leukotriene B<SUB>4</SUB> (LTB<SUB>4</SUB>)-induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently than aminophylline. Both drugs inhibited antigen and phospholipase A<SUB>2</SUB>-induced histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced O<SUB>2</SUB><SUP>1</SUP> generation from guinea pig alveolar macrophages. These results indicate that MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or LTB<SUB>4</SUB>-induced inflammatory reactions in guinea pigs and the allergic cutaneous reactions in rats when compared to aminophylline.
- 公益社団法人 日本薬理学会の論文
著者
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Yamaguchi Shuji
Department Of Biological Science Faculty Of Science Kumamoto University
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IWAMA Takehisa
Department of Pharmacology, Gifu Pharmaceutical University
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SAKURAI Toshimi
Department of Pharmacology, Gifu Pharmaceutical University
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Sakurai Toshimi
Department Of Pharmacology Gifu Pharmaceutical University
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Iwama Takehisa
Department Of Pharmacology Gifu Pharmaceutical University
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Koda Akihide
Department Of Pharmacology Gifu College Of Pharmacy
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KITAGAKI Kunihiko
Department of Hygiene, Dokkyo University School of Medicine
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Inagaki Naoki
Departmen T Of Pharmacology Gifu Pharmaceutical University
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Nagai Hiroichi
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Kitagaki Kunihiko
Department of Pharmacology, Gifu Pharmaceutical University
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