Time-dependent changes in inhibitory action of lipopolysaccharide onintestinal motility in rat

Journal of Veterinary Medical Science

Hiroshi OZAKI¹  Masatoshi HORI¹  Yasuhiro OHTA¹  Takahisa MURATA²  Md Shafiqul ISLAM¹  Noriyuki KAJI¹  Shoma MIKAWA¹ 

[1] 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;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

关键词: ileum;    inducible nitric oxide synthase;    lipopolysaccharide;    macrophage;    prostaglandin E2;   

DOI  :  10.1292/jvms.15-0198

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(32)Cited-By(1)Endotoxin causes gastrointestinal motility disorder. Aim of this study is to clarifyinhibitory mechanisms of lipopolysaccharide (LPS) on smooth muscle contraction in ratileum. Ileal tissues were isolated from control rat or from LPS-induced peritonitis modelrat. Treatment with LPS inhibited carbachol (CCh)-mediated contraction in a time-dependentmanner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes werealso upregulated, but iNOS expression was preceded by a rising of COX-2. All subtypes ofprostaglandin 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 1and 2 hr, but reduced the inhibitory action at 4 hr after the LPS treatment. COX-2inhibitor reversed the inhibitory action by LPS in all exposure time. Finally, in ilealtissues isolated from peritonitis model rat, iNOS expression was upregulated only at 4 hrafter LPS administration, resulting in enhanced inhibitory action of LPS againstCCh-induced contraction. In conclusion, LPS induces COX-2 to produce PGE2,which initially activates EP2 and/or EP4 on smooth muscle cells to inhibit thecontractility 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. Theinhibitory cascade is similar in the ileum isolated from peritonitis model rat, indicatingtime-dependent changes of inhibitory action by LPS on intestinal motility inperitonitis.

【 授权许可】

Unknown