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EFFECTS OF ANESTHETICS ON TRANSMISSION IN CNS

Research Project

Project/Area Number 11307049
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

IKEMOTO Yoshimi  Kyushu University Faculty of Dental Science, Prof., 歯学研究院, 教授 (90091272)

Co-Investigator(Kenkyū-buntansha) ITO Shinichi  Faculty of Dental Science, Ass. Prof., 歯学研究院, 助手 (00315095)
YOSHIDA Atsuya  Faculty of Dental Science, Ass. Prof., 歯学部付属病院, 講師 (00284521)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥30,410,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2002: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2001: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥16,800,000 (Direct Cost: ¥16,800,000)
Keywordsanesthetics / central neurons / neurontransmission / calcium ion concentration / miniature presynaptic current / histamine / mast cells / methyl paraben / 細胞Ca濃度 / Gly / ATP反応 / グルタミン酸 / グリア細胞 / 神経細胞 / シナプスブトン / 全身麻酔薬 / 細胞内カルシウム / パッチクランプ法 / 揮発性麻酔薬
Research Abstract

It is known that general anesthetics increase the GABA-A response in the CNS, resulting in augmentation of inhibitory transmission. Human recombinant GABA-A receptors were expressed in Sf9 cells and subunit specific effects of isoflurane were found, indicating that volatile anesthetics interact with membrane channel proteins to induce anesthesia in humans.
We dissociated central neurons of the rat, which had presysaptic terminals (boutons) attached. Under voltage clamp of these neurons, miniature EPSCs were recorded. Isoflurane increased the frequency, not amplitude of the glycinergic mIPSC. The increase was observed in both the presence and absence of external calcium ions, suggesting that the calcium concentration in the bouton was increased via release from the intracellular store sites.
ATP acts as an excitatory neurotransmitter via P2X receptors in peripheral and central nervous system. In DRG neurons of the rat, we identified slow and fast decaying ATP currents, which were due to activation of P2X2 and P2X3 receptor subtypes, respectively. Ketamine had no effects on the ATP currents. Propofol reduced the peak amplitude of the fast type current and accelerated the decay of the slow type current in the presence of ATP. Pentobarbital decreased the fast type current more potently than the slow type. The reduction was greater in less acidic environment, suggesting that ionized form of the agent was responsible for the effect.
Methyl paraben is contained as preservative in local anesthetic cartridges for dental use. Methyl paraben increased the intracellular concentration of rat peritoneal mast cells, probably via IP3 production. When PKA was activated somehow, the agent enhanced the release of histamine from the mast cells. This finding suggests that methyl paraben may induce anaphylactoid reactions in clinical practice.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Yamashita M, Ikemoto Y, Nielsen M, Yano T: "Effects of isoflurane and hexafluorodiethyl ether on human recombinant BAGA-A receptors expressed in Sf9 cells"European Journal of Pharmacology. 378(2). 223-231 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita M, Ueno T, Akaike N, Ikemoto Y: "Modulation of miniature inhibitory postsynaptic currents by isoflurane in rat dissociated neurons with glycinergic synaptic boutons"European Journal of Pharmacology. 431(3). 269-276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 北原誠子, 山下恵, 池本清海: "ラット脊髄後根神経節細胞のP2X受容体に対するケタミンとプロポフォルの作用"日本歯科麻酔学雑誌. 31(1). 11-16 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukugasako S, Ito S, Ikemoto Y: "Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells"British Journal of Pharmacology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita M, Ikemoto Y, Nielsen M, Yano T: "Effects of isoflurane and hexafluorodiethyl ether on human recombinant GABA-A receptors expressed in Sf9 cells"Eur J Pharmacol. 378. 223-231 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita M, Ueno T, Akaike N, Ikemoto Y: "Modulation of miniature inhibitory postsynaptic currents by isoflurane in rat dissociated neurons with glycinergic synaptic boutons"Eur J Pharmacol. 431. 269-276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitahara S, Yamashita M, Ikemoio Y: "Effects of ketamine and propofol on P2X receptors of rat DRG neurons"J JPN Dent Socie Anesth. 31. 11-16 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukugasako S, Ito S, Ikemoto Y: "Effects of methyl hydroxybenzoate (methyl paraben) on calcium ion concentration and histamine release in rat peritoneal mast cells"Br J Pharmacol. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita M, Kimono Y, Nielsen M, Yano T: "Effects of isoflurane and hexafluorodiethyl ether on human recombinant BAGA-A receptors expressed in Sf9 cells"European Journal of Pharmacology. 378(2). 223-231 (1999)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita M, Ueno T, Akaike N, Ikemoto Y: "Modulation of miniature inhibitory postsynaptic currents by isoflurane in rat dissociated neurons with glycinergic synaptic boutons"European Journal of Pharmacology. 431(3). 269-276 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 北原誠子, 山下恵, 池本晴海: "ラット脊髄後根神経節細胞のP2X受容体に対するケタミンとプロポフォルの作用"日本歯科麻酔学雑誌. 31(1). 11-16 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukugasako S, Ito S, Ikemoto Y: "Effects of methyl p-hydroxybenzoate (methyl Paraben) on Ca2^+ concentration and histamine release in rat peritoneal mast cells"British Journal of Pharmacology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita M, Ueno T, Akaike N, Ikemoto Y.: "Modulation of miniature inhibitory postsynaptic current by isoflurane in rat dissociated neurons with glycinergic synapse boutons"European Journal of Pharmacology. 431. 269-276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M,Yamashita,Y,Ikemoto,M,Nielsen,T,Yano: "Effects of isoflurane and hexaflurodiethyl ether human recombinant GABA-A receptors expressed in Sf9 cells."Eur,J,Pharmadology. 378. 223-231 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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