Effect of AA-861, a selective 5-lipoxygenase inhibitor, on models of allergy in several species.
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概要
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The effects of 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoquinone (AA-861), a selective 5-lipoxygenase inhibitor, on immunological or non-immunological release of slow reacting substance of anaphylaxis (SRS-A) and histamine and its effects on experimental asthma were investigated. AA-861 showed a dose-dependent inhibition of SRS-A release, with no effect on histamine release from passively sensitized guinea pig, monkey (<I>M. irus</I>) and human lung fragments. An analysis of the anaphylactic diffusate from the human lung fragments, using the combined technique of high performance liquid chromatography and radioimmunoassay, revealed that AA-861 markedly suppresses biosynthesis of the leukotrienes. However, this drug inhibits the release of histamine as well as SRS-A from lung fragments of anaphylactic monkey (<I>M. mulatta</I>) and in the Ca ionophore-stimulated rat peritoneal cavity. AA-861 suppressed the anaphylactically-induced airway resistance in mepyramine- and cimetidine-treated guinea pigs. These results suggest that AA-861 may be clinically effective for treating allergy-related asthma by modulating the 5-lipoxygenase pathway and that an inhibitory mechanism of histamine release by AA-861 may be present in some species.
- 公益社団法人 日本薬理学会の論文
著者
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Ohata Katsuya
Department Of Pharmacology Kyoto Pharmaceutical University:department Of Pneumology Ogaki Municipal
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Yamamura Hideki
Department Of Anatomy Hiroshima University School Of Medicine
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Kohno Shigekatsu
Department Of Pharmacology Division Of Pathological Sciences Kyoto Pharmaceutical University
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TAIRA Masafumi
Department of Pharmacology, Kyoto Pharmaceutical University
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NEGI Hideo
Department of Pharmacology, Kyoto Pharmaceutical University
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NANBU Fumio
Department of Pharmacology, Kyoto Pharmaceutical University
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