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1991 Fiscal Year Final Research Report Summary

Intracellular mediators in the process of secretory diarrhea

Research Project

Project/Area Number 01480229
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

MIURA Soichiro  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50138012)

Co-Investigator(Kenkyū-buntansha) SERIZAWA Hiroshi  Keio University, School of Medicine, Instructor, 医学部, 助手 (60187870)
SUEMATSU Makoto  Keio University, School of Medicine, Instructor, 医学部, 助手 (00206385)
YOSHIOKA Masahiro  Minamitama Hospital, Dept. of Medicine, 消化器内科, 医長 (10129728)
Project Period (FY) 1989 – 1991
KeywordsSecretory Diarrhea / Hemorrhagic diarrhea / Cholera toxin / Verotoxin / Intracellular calcium / Brush border enzyme / Microcirculation / Leukocyte
Research Abstract

Changes of intracellular mediators were determined in the process of secretory and hemorrhagic diarrhea induced by various kinds of bacterial toxins. The following results were obtained;
1) Cholera toxin (CT), heat labile toxin (LT) from E. coli, clostridium difficile toxin were administered into the jejunal loop of rats. CT and LT both activated A-kinase in the intestinal epithelial cells, while clostridium toxin induced secretory diarrhea via mechanism of Ca^<++>-mediated processes. But there is possibility that cytosolic free Ca^<++> of epithelial cells may play a role after A-kinase was activated in the process of CT-induced secretory diarrhea.
2) Increased activity of brush-border enzyme alkaline phosphatase (ALP) was recognized in CT-induced secretory diarrhea. In order to see the relation between membrane component which was specifically phosphorylated by CT and bush border ALP, phosphorylated fraction was compared with this BBM enzyme. The phosphorylated fraction was recognized t … More o be a 105KDa protein, which was different from ALP as determined by specific antibody against ALP.
3) The alteration of Ca^<++> concentration was determined in intestinal epithelial cells, endothelial cells and leukocytes under fluorescence microscopy. Clostridium toxin and verotoxin (VT) was shown to increase free Ca^<++> concentration in leukocytes, while CT did not influence the Ca^<++> concentration of leukocytes.
(4) Diameter, flow velocity and vascular permeability of intestinal microvessels were observed under intravital microscopy. After CT administration, enlargement of venules and increased blood flow were observed accompanying with the increased vascular permeability. Clostridium toxin and VT induced the decrease in blood flow and also induced leukocyte sticking in venules and hemorrhagic lesions in the intestinal mucosa. These lesions were inhibited by PAF- and Ca^<++>- antagonist suggesting that various vasoactive substances and leukocytes play major roles in the development of hemorrhagic diarrhea. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] S.Miura et al.: "Alkaline phosphatase of rat intestinal lymph:its characterization and the effect of fat administration." Clinica Chimica Acta.186. 239-248 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H,Tashiro,S.Miura et al: "Involvement of microcirculatory disturbances in verotoxin(VT)-induced hemorrhagic enteritis." Microcirculation Annual 1990. 111-112 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Miura et al: "Microcirculatory disturbance in indomethacin-induced intestinal ulcer." American Journal of Physiology. 261. G213-G219 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Miura et al: "Ischemic bowel necrosis induced by endothelin-1:An experimental model in rats." Digestion. 48. 163-172 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Miura et al.: "Advances in Research on Cholera and Related Diarrhea vol7.Effect of calcium antagonists on cholera-toxin induced secretory diarrhea" KTK Scientific Publishers, 93-98 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Miura et al.: "Advances in Research on Cholera and Related Diarrhea Heamorrhagic lesions induced by verotoxin from E.coli0157:H7 in rat small intestine." KTK Scientific Publishers, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura S, Yoshioka M, Hamada Y, Morita A, Asakura H, Tsuchiya M.: "Alkaline phosphatase of rat intestinal lymph: its characterization and the effect of fat administration." Clinica Chimica Acta. 186. 239-248 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tashiro H, Miura S, Serizawa H, Yoshioka M, Tanaka S, Asako H, Suematsu M, Kurose I, Tsuchiya M, Kudoh Y: "Involvement of microcirculatory disturbance in verotoxin-induced hemorrhagic enteritis." Microcirculation Annual. 1990. 111-112 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura S, Tanaka S, Yoshioka M, Hamada Y, Morishita T, Asakura H, Tsuchiya M.: "Effect of calcium antagonists on choleratoxin induced secretory diarrhea." Advances in research on cholera and related diarrheas. Vol 7 eds. by Sack RB, Zinnaka Y. KTK Scientific Publishers, Tokyo. 93-98 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura S, Suematsu M, Tanaka S, Nagata H, Houzawa S, Suzuki M, Kurose I, Serizawa H, Tsuchiya M.: "Microcirculatory disturbances in indomethacininduced intestinal ulcer." American Journal of Physiology. 261. G213-G219 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura S, Kurose I, Fukumura D, Suematsu M, Sekizuka E, Tashiro H, Serizawa H, Asako H, Tsuchiya M.: "Ischemic bowel necrosis induced by endothelin-l: An experimental model in rats." Digestion. 48. 163-172 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura S, Tashiro H, Yoshioka M, Tanaka S, Serizawa H, Kurose I, Sekizuka E, Suematsu M. Tsuchiya M, Kai A, Kudoh Y, Ohashi M.: "Hemorrhagic lesions induced by verotoxin from E. coli 0157:H7 in rat small intestine." Advances in research on cholera and related diarrheas. (1991)

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

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Published: 1994-03-18  

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