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1988 Fiscal Year Final Research Report Summary

The mechanism of hypersensitization in diabetic state of neuromuscular synapse to depolarizing blockers

Research Project

Project/Area Number 62480118
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionToyama Medical & Pharmaceutical University

Principal Investigator

KIMURA Masayasu  Professor, Dept. of Chemical Pharmacol., 薬学部, 教授 (60019099)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Shinjiroh  Research Assistant, Dept. of Chemical Pharmacol., 薬学部, 助手 (10186744)
KIMURA Ikuko  Associate Prof., Dept. of Chemical Pharmacol., 薬学部, 助教授 (70019131)
Project Period (FY) 1987 – 1988
Keywordsdiabetic state / muscle cell membrane / intracellular Ca^<2+> mobilization / site of action of succinylcholine / potentiation mechanism of -eudesmol / diabetic state-induced modification of intracellular Ca^<2+> mobilization / 糖尿病態による細胞内Ca動員 / Ca誘発脱感作
Research Abstract

The aim of this study was to investigate the diabetic state-induced potentiation of depolarizing inhibition by using the pharmacological prode found from traditional Sino-Japanese medicines. The following results were obtained from the last two years.
1. The diabetic state-induced modification of muscle cell membranes were to lower resting membrane potentials, to decrease membrane conductance and to inhibit Ca^<2+> influx.
2. The occurrence of diabetic state converted the mode of succinylcholine-binding action from positive to negative one. The distribution of Ca^<2+> was concentrated in muscle tissues. This evidence was supported by increasing activity of Ca^<2+>.
3. The new Ca^<2+> mobilization was observed by the treatment with anti-cholinesterase, and was not accompanied by contraction of muscles. The Ca^<2+> mobilization was inhibited by low concentrations of d-tubocurarine, but not by succinylcholine. The result of patch clamp experiments showed that succinylcholine-activated single channel condictance was inhibited by high concentrations of external Ca^<2+>.
4. -Eudesmol, the constituent of atractylodes lancea, potentiated succinylcholineinduced blocking effect of neuromuscular synapse. The synapse in diabetic state was inhibited more increasingly by -eudesmol.
From the above results, we concluded that diabetic state-induced potentiation to depolarizing blockers may be caused by Ca^<2+>-dependent desensitization of neuromuscular synapse.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kimura,I.;Kondoh,T.;Kimura,M.: Nature,New Biology. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,I.;Kondoh,T.;Kimura,M.: Neuropharmacology. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,I.;Nojima,H.;Kimura,M.: Pfluger Archiv. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muroi,M.;Tanaka,K.;Kimura,I.;Kimura,M.: Japan.J.Pharmacol.(1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.;Kobayashi,S.;Fujihara,M.;Hoshino,N.;Kimura,I.: Endocrinologia Japonica. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,I.;Nakamura,T.;Kimura,M.: Japan.J.Pharmacol.47. 197-199 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.;Kimura,I.;Nakamura,T.;Nojima,H.: Diabetologia. 31. 103-107 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.;Kimura,I.;Fujihara,M.;Hoshino,N.: Life Sciences. 42. 1029-1036 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.;Kobayashi,S.;Nakagawa,M.;Kimura,I.: Endocrinologia Japonica. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木村正康,木村郁子,松井哲夫,古林伸二郎: "遺伝性肥満型糖尿病マウスKK-CA^ソの病態薬理学的特色ーアロキサンおよびストレプトゾトシン糖尿病マウスとの比較ー糖尿病動物第2巻" 医薬ジャーナル社, 138-147 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,I.;Kimura,M.: "Modification of Ca^<2+>transients by diabetes and denervation in mouse diaphragm muscles stimulated directly.In Polyol Pathway and Its Role in Diabetic Complications.ed.by Sakamoto" Elsevier Science, 502-504 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,I.;Kimura,M.: "Modification of Ca^<2+>transients by diabetes and denervation in mouse diaphragm muscles stimulated directly.In Polyol Pathway and Its Role in Diabetic Complications." Elsevier Science., 502-504 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura I; Kondoh T; Kimura M: "Postsynaptic nicotinic ACh receptor-operated intracellular Ca^<2+> release" Nature, New Biology. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura I; Kondoh T; Kimura M: "ACh receptor-mediated alteration of intracellular Ca^<2+> release" Neuropharmacology. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura I; Nojima H; Kimura M: "Ca^<2+>-dependence of acetylcholine receptor-channel conductance at endplates of muscle cells of adult mouse" Pfluger Archiv. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muroi M; Tanaka K; Kimura I; Kimura M: " -eudesmol (a main component of atractylodes lancea)-induced potentiation of depolarizing neuromuscular blockade in diaphragm muscles of normal and diabetic mice" Japan. J. Pharmacol.(1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura M; Kobayashi S; Fujihara M; Hoshino N; Kimura I: "Diabetic state-induced activation of calcium-activated neutral proteinase in mouse skeletal muscle" Endocrinologia Japonica. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura I; Nakamura T; Kimura M: "Alloxan-diabetic state-induced suppression of Ca^<2+>dependent slow action potentials in mouse diaphragm muscle" Japan. J. Pharmacol.47. 197-199 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura M; Kimura I; Nakamura T; Nojima H: "Diabetic state-induced modification of resting membrane potential and conductance in diaphragm muscle of alloxan and diabetic KK-CA^y mice" Diabetologia. 31. 103-107 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura M; Kimura I; Fujihara M; Hoshino N: "Diabetic state-induced modifications of succinylcholine binding mode in the microsomal fractions of mouse skeletal muscles" Life Sciences. 42. 1029-1036 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura M; Kobayashi S; Nakagawa M; Kimura I: "Diabetic state-induced modification of contents of Ca, Mg, Fe and Zn in skeletal, cardiac and smooth muscles of mice" Endocrinologia Japonica. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura I; Kimura M; Kimura M: Modification of Ca^<2+> transients by diabetes and denervation in mouse diaphragm muscles stimulated directly. In Polyol Pathway and Its Role in Diabetic. Complications, Elsevier Science, 502-504 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura M; Kimura I: Neuromuscular disorders in the diabetic mouse : Effects of junction blockers. In Recent Trends in Management of Diabetes Mellitus.Elsevier Science, 409-412 (1987)

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

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Published: 1990-03-20  

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