Role of Leukotriene B4 in 5-Lipoxygenase Metabolite- and Allergy-Induced Itch-Associated Responses in Mice

• Tsuji Fumio

  Research and Development Center, Santen Pharmaceutical Co., Ltd. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University

• Aono Hiroyuki

  Research and Development Center, Santen Pharmaceutical Co., Ltd.

• Tsuboi Takashi

  Research and Development Center, Santen Pharmaceutical Co., Ltd.

• Murakami Tadahiro

  Research and Development Center, Santen Pharmaceutical Co., Ltd.

• Enomoto Hiroshi

  Research and Development Center, Santen Pharmaceutical Co., Ltd.

• Mizutani Keiko

  Research and Development Center, Santen Pharmaceutical Co., Ltd.

• Inagaki Naoki

  United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University

抄録

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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 33 (6), 1050-1053, 2010

  公益社団法人 日本薬学会

キーワード

• leukotriene B₄
• scratching behavior
• passive cutaneous anaphylaxis
• SA6541
• leukotriene A₄ hydrolase

詳細情報

• CRID: 1390282679605040896
• NII論文ID: 130000247978
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.33.1050
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 10689450
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10689450
• Web Site: http://www.jstage.jst.go.jp/article/bpb/33/6/33_6_1050/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010310626
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可