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标题：Role of Leukotriene B4 in 5-Lipoxygenase Metabolite- and Allergy-Induced Itch-Associated Responses in Mice
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作者：Fumio Tsuji ; Hiroyuki Aono ; Takashi Tsuboi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：6
页码：1050-1053
DOI：10.1248/bpb.33.1050
出版社：The Pharmaceutical Society of Japan
摘要：We investigated the role of leukotriene (LT) B₄ in 5-lipoxygenase metabolite- and allergy-induced itch-associated responses using SA6541, an LTA₄ hydrolase inhibitor. Itch-associated responses were induced by intradermal injection of 5-hydroperoxyeicosatetraenoic acid (HPETE), a precursor of 5-lipoxygenase metabolites, and passive cutaneous anaphylaxis in ICR mice. By screening molecules related to arachidonic acid metabolism or pruritus, SA6541 was found to be a specific inhibiter of LTA₄ hydrolase. Pharmacokinetic studies confirmed the specificity of SA6541 at an oral dose of 100 mg/kg in mice. 5-HPETE induced scratching behavior, which was inhibited by SA6541 (100 mg/kg). However, SA6541 (100 mg/kg) hardly attenuated the 5-HPETE-induced increase in vascular permeability. Moreover, SA6541 (100 mg/kg) partially attenuated scratching behavior, but did not affect the increase in vascular permeability caused by passive cutaneous anaphylaxis. On the other hand, ketotifen fumarate, a histamine H1 antagonist, strongly inhibited the scratching behavior and the increase in vascular permeability caused by passive cutaneous anaphylaxis. These results suggest that LTB₄ is an endogenous itch mediator in the skin and is involved in the pruritus response in allergic reactions.
关键词：leukotriene B4;scratching behavior;passive cutaneous anaphylaxis;SA6541;leukotriene A4 hydrolase