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2003 Fiscal Year Final Research Report Summary

Regulation of GI motility by cross-talk with nerve, pace maker anti immune cells

Research Project

Project/Area Number 13306023
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

HORI Masatoshi  The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (70211547)

Co-Investigator(Kenkyū-buntansha) MOMOTANI Eiichi  National Institute of Animal Health, Chief researcher, 室長(研究職) (50355145)
SATO Koichi  Yamaguchi University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90205914)
OZAKI Hiroshi  The University of Tokyo, Graduate School of Agriculture and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (30134505)
KARAKI Hideaki  Azabu University, Department of Veterinary Medicine, Visiting Professor, 獣医学部, 客員教授
HIKONO Hirokazu  National Institute of Animal Health, Researcher, 研究員 (60355146)
Project Period (FY) 2001 – 2003
Keywordsmacrophage / gut motility / inflammation / prostaglandins / smooth muscle / contraction / nitric oxide / IL-1β
Research Abstract

Intestinal motility is under the control of several systems, including the neurogenic, myogenic and endocrine systems. Morphological and functional studies in recent years have suggested that interstitial cells of Cajal (ICCs) are pacemakers in the musculature of the gastrointestinal tract. ICCs are arranged in distinctive patterns in close relation to nerve and smooth muscle cells in the muscle layer, and generate pacemaker currents to develop electrical slow waves in the gastrointestinal smooth muscles. In addition, muscularis resident macrophages are regularly distributed in the subserosa and at the level of the myenteric plexus. However, it remains to be determined how these cells coordinately contribute to the GI motility. In this study, we have obtained the following results :
1)Inhibition of spontaneous contractions and peristalsis in circular smooth muscle from the colons of Crohn's disease model (TNBS-treated) rats is attributable to the impairment of ICCs and myenteric nerve systems. The indication of macrophage activation and the close correlation between the degeneration and macrophage accumulation suggest that the macrophages play critical a role in the degenerative pathology of intestinal motility.
2)Decrease in the contraction of circular smooth muscle isolated from TNBS induced colitis rat colon is attributable to the decreased activity of the L type Ca-channel. The dysfunction of the L type Ca-channel may be mediated by NF-κB-dependent pathways.
3)Treatment, of smooth muscle with IL-1□, which is derived mainly from macrophages, decreases either CPI-17 expression or MYPT I phosphorylation, which results in an increase in myosin phosphatase activity to reduce force generation. IL-1□ could be an important mediator of gastrointestinal motility disorders in IBD, etc.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] M.Hori, M.Kita, S.Torihashi, S.Miyamoto, K.-J.Won, H.Ozaki, H.Karaki: "Up-regulation of iNOS by COX-2 in muscularis resident macrophage of rat intestine stimulated with LPS"Am.J.Physiol.. 280. G930-G938 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata T, Yamawaki H, Hori M, Sato K, Ozaki H, Karaki H: "Hypoxia impairs endothelium-dependent relaxation in organ cultured pulmonary artery."Eur.J.Pharmacol.. 421. 45-53 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata T, Sato K, Hori M, Ozaki H, Karaki H: "Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension."J.Biol.Chem.. 277. 44085-44092 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka T, Sato K, Hori M, Ozaki H, Karaki H: "FcεRI cross-linking-induced actin assembly mediates calcium signalling in RBL-2H3 mast cells."Br.J.Pharmacol.. 136. 837-846 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka T, Sato K, Hori M, Ozaki H, Karaki H: "Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3 mast cells."Br.J.Pharmacol.. 135. 1959-1966 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki H, Hori M, Kim YS, Kwon SC, Ahn DS, Nakazawa H, Kobayashi M, Karaki H: "Inhibitory mechanism of xestospongin-C on contraction and ion channels in the intestinal smooth muscle."Br.J.Pharmacol.. 137. 1207-1212 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K-J Won, S Torihashi, M Mitsui-Saito, M Hori, K Sato, T Suzuki, H Ozaki, H Karaki: "Increased smooth muscle contractility of intestine in the genetic null of the endothelin ETB receptor, a rat model for long-segment Hirschsprung's disease"Gut. 50. 355-360 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kinoshita K, Sato K, Hori M, Ozaki H, Karaki H: "Decrease in the activity of the smooth muscle L-type Ca^<2+>-channels and its reversal by NF-κB inhibitors in Crohn's colitis model"Am.J.Physiol.. 285. G483-G493 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohama T, Hori M, Sato K, Ozaki H, Karaki H: "Chronic treatment with IL-β attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle"J.Biol.Chem.. 278. 48794-48804 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki H, Kawai T, Won KJ, Suzuki T, Sato K, Horiguchi H, Hori M, Karaki H, Torihashi S, Ward S, Sanders KM: "Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine."Neurogastroenterology and Motility. 16. 39-51 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka T, Hori M, Tanaka A, Matsuda H, Karaki H, Ozaki H: "IgE alone-induced actin assembly modifies calcium signaling and degranulation in RBL-2H3 mast cells."Am J Physiol. 286. C256-C263 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki H, Karaki H: "Organ culture as a useful method for studying the biology of blood vessels and other smooth muscle tissues. (Review)"Jpn J Pharmacol. 89. 93-100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hori M, Kita M, Torihashi S, Miyamoto S, Won KJ, Sato K, Ozaki H, Karaki H: "Upregulaiion of iNOS by COX-2 in niuscularis resident macrophage of rat intestine stimulated with LPS."Am J Physiol. 280. G930-G938 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murata T, Yamawaki H, Hori M, Sato K, Ozaki H, Karaki H: "Hypoxia impairs endothelium-dependent relaxation in organ cultured pulmonary artery."Eur J Pharniacol. 421. 45-53 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murata T, Sato K, Hori M, Ozaki H, Karaki H: "Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension."J Biol Chem. 277. 44085-44092 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka T, Sato K, Hori M, Ozaki H, Karaki H: "FcεRI cross-linking-induced actin assembly mediates calcium signalling in RBL-2H3 mast cells."Br J Pharmacol. 136. 837-846 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka T, Sato K, Hori M, Ozaki H, Karaki H: "Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3 mast cells."Br J Pharnracoy. 135. 1959-1966 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki H, Hori M, Kim YS, Kwon SC, Aim DS, Nakazawa H, Kobayashi M, Karaki H: "Inhibitory mechanism of xestospongm-C on contraction and ion channels in the intestinal smooth muscle."Br J Pharrnacoy. 137. 1207-1212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Won KJ, Torihashi S, Mitsui-Saito M, Hori M, Sato K, Suzuki T, Ozaki H, Karaki H: "Increased smooth muscle contractility of intestine in the genetic null of the endothelin ET_B receptor : a rat model for long segment Hirschsprung's disease."Gut. 50. 355-360 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kinoshita K, Sato K, Hori M, Ozaki H, Karaki H: "Decrease in the activity of the smooth muscle L-type Ca^<2+>-channels and its reversal by NF-κB inhibitors in Crohn's colitis model."Am J Physiol. 285. G483-G493 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohama T, Hori M, Sato K, Ozaki H, Karaki H: "Chronic treatment with IL-β attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle."J.Biol.Chem. 278. 48794-48804 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki H, Kawai T, Won KJ, Suzuki T, Sato K, Horiguchi H, Hori M, Karaki H, Torihashi S, Ward S, Sanders KM: "Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine."Neurogastroenterology and Motility. 16. 39-51 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka T, Hori M, Tanaka A, Matsuda H, Karaki H, Ozaki H: "IgE alone-induced actin assembly modifies calcium signaling and degranulation in RBL-2H3 mast cells."Am J Physio. 286. C256-C263 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki H, Karaki H: "Organ culture as a useful method for studying the biology of blood vessels and other smooth muscle tissues. (Review)"Jpn J Pharillacol. 89. 93-100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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