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Spontaneous relaxation of isolated smooth muscle cells shortened with muscarinic receptor stimulation

Research Project

Project/Area Number 07457544
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionMEIJI COLLEGE OF PHARMACY

Principal Investigator

UCHIDA Masaatsu  MEIJI COLLEGE OF PHARMACY FACULTY OF PHARMACY PROFESSOR, 薬学部, 教授 (90097197)

Co-Investigator(Kenkyū-buntansha) OISHI Kazuhiko  MEIJI COLLEGE OF PHARMACY FACULTY OF PHARMACY RESEARCH ASSOCIATE, 薬学部, 助手 (80203701)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordsrelaxation / protein kinase C / guinea-pig stomach / smooth muscle cells / streptolysin-O / permeabilize / acetylcholine / actin / 自然弛緩 / 収縮 / ムスカリ受容体 / 平滑筋 / 培養細胞 / 分化 / ムスカリン受容体 / 張力 / カルシウムイオン / 膜透過性
Research Abstract

Contracted smooth muscle relaxs spontaneously when contractile agonist is removed. In this study, we have provide first evidence that muscarinic receptor-mediated activation of PKC in the process of ACh-induced cell shortening is necessary for the subsequent relaxation of the shortened cells. This study was done with streptolysin-O-permeabilized single smooth muscle cells by measuring cell shortening under the condition without any tension load.
PKC-dependent relaxation mechanism was found to be specific for the contractile stimulation of muscarinic receptors. Moreover, the receptor-mediated activation of PKC in the process of ACh-induced cell shortening was required for the subsequent relaxation of the shortened cells. Thus, it is likely that PKC-dependent promotion stage is required for the subsequent relaxation which is triggered by removal of contractile stimulant ACh and fall of free Ca^<2+>. In contrast, the relaxation from Ca^<2+>-induced cell shortening was independent on PKC.Th … More e differences in PKC-dependence could be due to the activation of muscarinic receptor-mediated metabotropic signaling.
It is unclear what is the mechanism underlying PKC-dependent promotion of relaxation. It is, however, most likely that PKC-dependent activation of regulatory mechanisms during agonist-induced contractions could be involved. Several possible regulatory mechanisms which are related to maintenance of tone and latch state are reported to be activated PKC-dependently. We focused one of these mechanisms, the reorganization of cytoskeleton. We have obtained several evidences that PKC regulation of actin cytoskeletal reorganization during contraction is responsible for subsequent relaxation from agonist-induced contraction.
Contracted smooth muscle tissues under the condition with tension-load were readily relaxd by a wash even if the contraction was induced by ACh in the presence of a protein kinase inhibitor. These results arise the possibility that the PKC-dependent relaxation mechanism, which actively participates in the relaxation of agonist-shortened individual smooth muscle cells, is apparently concealed by the tension-related relaxation in the preparation of tension-loaded whole tissues.
In conclusion, we demonstrated a novel mechanism of smooth muscle relaxation. It is suggested that PKC-dependent reorganization of actin cytoskeleton during agonist-induced contraction promotes spontaneous relaxation. Less

Report

(3 results)
  • 1997 Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Y.Miyauchi, K.Oishi, and M.K.Uchida.: "Ca^<2+>-inhibition of Ca^<2+>-induced small contraction of rat uterine smooth muscle." Eur.J.Pharmacol.263. 75-80 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Miyauchi, K.Oishi, and M.K.Uchida: "Actin-severing and Ca^<2+>-induced reversal of smooth muscle contraction independent of Ca^<2+>" Gen.Pharmacol.25. 691-695 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Inoue, A.Sakurai, H.Tuga, K.Oishi, and M.K.Uchida.: "Carbachol-induced desensitization of rat basophilic leukemia(RBL-2H3)cells transfected with human m3 muscarinic acetylcholine receptors." Gen.Pharmacol.26. 1125-1131 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.G.Yonei, K.Oishi, and M.K.Uchida: "Regulation of exocytosis by the small GTP-binding protein Rho in rat basophilic leukemia(RBL-2H3)cells." Gen.Pharmacol.26. 1583-1589 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Mita, K.Satoh-Akimoto, K.Oishi, T.Hashimoto and M.K.Uchida: "Inhibition of muscarinic receptor-operated Ca^<2+> sensitization by short-term desensitization of α-toxin-permeabilized smooth muscle cells from guinea-pig stomach." Gen.Pharmacol.29. 753-761 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.K.Uchida: "Smooth muscle contraction" Kohama,K.and Saida,K.,Japan Sci,Soc,Press,Tokyo, 39-68 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Oishi and M.K.Uchida: "Receptor desensitization and Ca-signaling" Uchida,M.K.,Japan Scientific press,Tokyo, 47-67 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yuuki Miyauchi, Kazuhiko Oishi, and Masaatsu K.Uchida.: "Ca^<2+>-inhibition of Ca^<2+>-induced small contraction of rat uterine smooth muscle." Eur.J.Pharmacol.263. 75-80 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yuuki Miyauchi, Kazuhiko Oishi, and Masaatsu K.Uchida.: "Actin-severing and Ca^<2+>-induced reversal of smooth muscle contraction independent of Ca^<2+>." Gen.Pharmacol.25. 691-695 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Rika Inoue, Akihiro Sakurai, Hirofumi Tuga, Kazuhiko Oishi, and Masaatsu K.Uchida.: "Carbachol-induced desensitization of rat basophilic leukemia (RBL-2H3) cells transfected with human m3 muscarinic acetylcholine receptors." Gen.Pharmacol.26. 1125-1131 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shuuji G.Yonei, Kazuhiko Oishi, and Masaatsu K.Uchida.: "Regulation of exocytosis by the small GTP-binding protein Rho in rat basophilic leukemia (RBL-2H3) cells." Gen.Pharmacol.26. 1583-1589 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsuo Mita, Koji Satoh-Akimoto, Kazuhiko Oishi, Takao Hashimoto and Masaatsu K.Uchida.: "Inhibition of muscarinic receptor-operated Ca^<2+> sensitization by short-term desensitization of alpha-toxin-permeabilized smooth muscle cells from guinea-pig stomach." Gen.Pharmacol.29. 753-761 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masaatsu K.Uchida.: "Ca^<2+>-induced actin-severing and contraction of smooth muscle." in 'Smooth muscle contraction'ed by Kohama, K.and Saida, K.Japan Sci, Soc, Press, Tokyo. 39-68 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuhiko Oishi and Masaatsu K.Uchida.: Diversity of desensitization of secretion in basophilic leukemia cells transfected with muscarinic receptor m2 and m3 subtypes. in 'Receptor desensitization and Ca-signaling' , ed by Uchida, M.K.Japan Scientific press, Tokyo, 47-67 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsuo Mita, Kazuhiko Oishi, Takao Hashimoto, and Masaatsu K.Uchida.: Threshold changes in muscarinic receptor-operated all-or-none response by desensitization in isolated smooth muscle cells from taenia caecum. in 'Receptor desensitization and Ca-signaling' , ed by Uchida, M.K.Japan Scientific press, Tokyo, 21-46 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mita,M.,Satoh-Akimoto,K,.Oishi,K.,Hashimoto,T.and Uchida,M.K.: "Inhibition of muscarinic receptor-operatedCa2^<2+>sensitization by short-term desensitization of α-toxin-permcabilized smooth muscle cells from guinca-pig stomach." General Pharmacology. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyauchi, Y., Oishi, K. and Uchida, M. K.: "Actin-severing and Ca^<2+> -induced reversal of smooth muscle contraction that is independent of Ca^<2+>" General Pharmacology. 25. 691-695 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yonei, S. G., Oishi, K. and Uchida, M. K.: "Regulation of exocytosis by the small GTP-binding protein Rho in rat basophilic leukemia (RBL-2H3) cells." General Pharmacology. 26. 1583-1589 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Oishi, K. and Uchida, M. K.: "Receptor desensitization and Ca-signaling" Uchida, M. K., Japan Scientific press, Tokyo, 213(p.47〜67) (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mita, M., Oishi, K., Hashimoto, T. and Uchida, M. K.: "Receptor desensitization and Ca-signaling" Uchida, M. K., Japan Scientific press, Tokyo, 213(p.21〜46) (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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