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2000 Fiscal Year Final Research Report Summary

Molecular mechanism of development of mammalian smooth mscle

Research Project

Project/Area Number 10470025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

NISHI Katsuhide  Kumamoto University, School of Medicine, Associate professor, 医学部, 教授 (00040220)

Co-Investigator(Kenkyū-buntansha) TOKUTOMI Yoshiko  Kumamoto University, School of Medicine, Assistant Professor, 医学部, 助手 (90253723)
TOKUTOMI Naofumi  Kumamoto University, School of Medicine, Associate professor, 医学部, 助教授 (30227582)
Project Period (FY) 1998 – 2000
Keywordsc-kit / development / smooth muscle / mouse / pacemaker / Ca^<2+> storage / intracellular Ca^<2+>
Research Abstract

c-kit, a receptor-type tyrosine kinase may regulate development of smooth muscle tissue in the mammalian gastrointestinal tract. To illustrate how c-kit plays roles in the functional development of the smooth muscle tissue, we surveyed change in the population and function of c-kit-positive (c-kit^+) cells, i.e. interstitial cells of Cajal, in the developing gastrointestinal tract of BALB/c mice intraperitoneally injected with the neutralizing anti-c-kit-monoclonal antibody (ACK2) for 8 days after birth. In control animals, the c-kit^+ cells constructed networks, contacting with both enteric nervous system and smooth muscle layers, but not in the ACK2-treated animals that had impaired spontaneous contractility of the intestine because of lack of the c-kit^+ cells. that possessed rhythmic Ca^<2+>-activated Cl^-conductance. It is also found that the c-kit^+ cells in the pacemaker region of the small intestine arid the longitudinal smooth muscle cells developed from the same kit-positive precursor cells, depending upon the extent of kit signals.
In smooth muscle cells dissociated from gastrointestinal tract of the ACK2-treated animals, dysfunction in the ryanodine-sensitive Ca^<2+> storage in the cytoplasm was suggested when tested with caffeine-induced Ca^<2+>-activated K^+ currents under voltage-clamp conditions and fura-2 fluorometric measurements of intracellular Ca^<2+> concentration. Altogether, it is suggested that c-kit plays important roles in regulating development of the function of mammalian gastrointestinal tract.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Liu, J., Lai, Z-F., Wang, X-D., Tokutomi, N., Nishi, K.: "Inhibition of sodium current by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in guinea pig cardiac ventricular cells"J.Cardiovasc.Pharmacol.. 31. 558-567 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lai, Z-F., Nishi, K.: "Intracellular chloride activity increases in guinea pig ventricular muscle during simulated ischemia"Am.J.Physiol.. 275. 1613-1619 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen, Y-Z., Lai, Z-F., Nishi, K., Y, Nishimura: "Modulation of calcium responses by altered peptide ligands in a human T cell clone"Eur.J.Immunol.. 28. 3929-3939 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugita, M., Tokutomi, N., Tokutomi, Y., Terasaki, H., Nishi, K.: "he properties of caffeine - and carbachol - induced intracellular Ca2+ release in mouse bladder smooth muscle cell"Euro.J.Pharmacol.. 348. 61-70 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami, M., Tokutomi, N., Tokutomi, Y., Tomita, K., Nishi, K.: "Alkalinization - induced K+ current of the mouse megakaryocyte"Jpn.J.Phamacol.. 79. 343-350 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Torihashi, S., Nishi, K., Tokutomi, Y., Nishi, T., Sean Ward, Kenton M.Sanders: "Blockade of Kit Signaling Induces Transdifferentiation of Interstitial Cells of Cajal to a Smooth Muscle Phenotype"GASTROENTEROLOGY. 117. 140-148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jie Liu, Kohji Fukunaga, Hideyuki Yamamoto, Katsuhide Nishi, Eishichi Miyamoto: "Differential Roles of Ca2+/Calmodulin-Dependent Protein Kinase II and Mitogen-Activated Protein Kinase Activation in Hippocampal Long-Term Potentiation"The Journal of Neuroscience. 19. 8292-8299 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokutomi N., Nishi K.: "the Effects of Mexiletine on the Activity of Neuronal Voltage-gated Na^+ channels"Jpn.Pharmacol & Therapeutics. 28. 133-141 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhong-Fang Lai, Yu-Zhen Chen, Yasuharu Nishimura, Katsuhide Nishi: "An Amiloride-Sensitive and Voltage-Dependent Na^+ Channel in an HLA-DR-Restricted Human T Cell Clone^1"The Journal of Immunology. 165. 83-90 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhong-Fang Lai, Katsuhide Nishi: "Enhancement of intracellular Cl^- concentrations induced by extracellular ATP in guinea pig ventricular muscle"Jpn.J.Pharmacol. 84. 438-448 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokutomi, Y., Tokutomi, N., Nishi K.: "The properties of ryanodine-sensitive Ca^2+ release in mouse gastric smooth muscle cells"British Journal of Pharmacology. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu, J.: "Inhibition of sodium current by chloride channel blocker4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in guinea pig cardiac ventricular cells"J.Cardiovasc.Pharmacol.. 31. 558-567 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lai, Z-F.: "Intracellular chloride activity increases in guinea pig ventricular muscle during simulated ischemia"Am.J.Physiol.. 275. 1613-1619 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen, Y-Z.: "Modulation of calcium response by altered peptide ligands in a human T cell clone"Eur.J.Immunol.. 28. 3929-3939 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugita, M.: "he properties of caffeine -and carbachol -induced -intracellular Ca2+ release in mouse bladder smooth muscle cell"Euro.J.Pharmacol.. 348. 61-70 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami, M.: "Alkalinization -induced K+ current of the mouse megakaryocyte"Jpn.J.Phamacol.. 79. 343-350 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Torihashi, S.: "Blockade of Kit Signaling Induces Transdifferentiation of Interstitial Cells of Cajal to a Smooth Muscle Phenotype"GASTROENTEROLOGY. 117. 140-148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jie Liu: "Differential Roles of Ca2+/Calmodulin-Dependent Protein Kinase II and Miotogen-Activated Protein Kinase Activation in Hippocampal Long-Term Potentiation"The Journal of Neuroscience. 19(19). 8292-8299 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokutomi, N.: "The Effects of Mexiletine on the Activity of Neuronal Voltage-gated Na^+ channels"Jpn.Pharmacol & Therapeutics. 28. 133-141 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhong-Fang Lai: "An Amiloride-Sensitive and Voltage-Dependent Na^+ Channel in an HLA-DR-Restricted Human T Cell Clone^1"The Journal of Immunology. 165. 83-90 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhong-Frang Lai: "Enhancement of Intracellular CL Concentrations Induced by Extracellular ATP in Guinea Pig Ventricurar Muscle"Jpn.J.Phamacol.. 84. 438-448 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokutomi. Y.: "The properties of ryanodine-sensitive Ca2+ release in mouse gastric smooth muscle cells"British Journal of Pharmacology. (in press). (2001)

    • 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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