Time-dependent changes in inhibitory action of lipopolysaccharide on intestinal motility in rat

• MIKAWA Shoma

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• OHTA Yasuhiro

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• KAJI Noriyuki

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• ISLAM Md Shafiqul

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• MURATA Takahisa

  Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• OZAKI Hiroshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

• HORI Masatoshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

抄録

Endotoxin causes gastrointestinal motility disorder. Aim of this study is to clarify inhibitory mechanisms of lipopolysaccharide (LPS) on smooth muscle contraction in rat ileum. Ileal tissues were isolated from control rat or from LPS-induced peritonitis model rat. Treatment with LPS inhibited carbachol (CCh)-mediated contraction in a time-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes were also upregulated, but iNOS expression was preceded by a rising of COX-2. All subtypes of prostaglandin E₂ (PGE₂) receptors (EP1-EP4) were expressed in ileum, and PGE₂ and selective EP2 or EP4 agonist inhibited CCh-mediated contraction. Selective iNOS inhibitor did not reverse LPS-induced inhibition of contraction by CCh at 1 and 2 hr, but reduced the inhibitory action at 4 hr after the LPS treatment. COX-2 inhibitor reversed the inhibitory action by LPS in all exposure time. Finally, in ileal tissues isolated from peritonitis model rat, iNOS expression was upregulated only at 4 hr after LPS administration, resulting in enhanced inhibitory action of LPS against CCh-induced contraction. In conclusion, LPS induces COX-2 to produce PGE₂, which initially activates EP2 and/or EP4 on smooth muscle cells to inhibit the contractility in early phase of LPS exposure. Moreover, in late phase of LPS treatment, iNOS is expressed to produce NO, which in turn inhibited the contraction by CCh. The inhibitory cascade is similar in the ileum isolated from peritonitis model rat, indicating time-dependent changes of inhibitory action by LPS on intestinal motility in peritonitis.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ 77 (11), 1443-1449, 2015

  公益社団法人 日本獣医学会

キーワード

• ileum
• inducible nitric oxide synthase
• lipopolysaccharide
• macrophage
• prostaglandin E₂

詳細情報

• CRID: 1390001206429769344
• NII論文ID: 130005112081
• NII書誌ID: AA10796138
• DOI: 10.1292/jvms.15-0198
• ISSN: 13477439
• ISSN: 09167250
• NDL書誌ID: 026964791
• PubMed: 26051129
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026964791
• Web Site: https://www.jstage.jst.go.jp/article/jvms/77/11/77_15-0198/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016144104
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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