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Contribution of L-type Voltage Sensitive Ca^<2+> Channels to Mechanism of General Anesthesia

Research Project

Project/Area Number 09470323
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionHirosaki University

Principal Investigator

HIROTA Kazuyoshi  University Hospital, Hirosaki University Instructor, 医学部・附属病院, 助手 (20238413)

Co-Investigator(Kenkyū-buntansha) OHKAWA Hirobumi  University Hospital, Hirosaki University Instructor, 医学部・附属病院, 助手 (40322953)
MIHOKO Kudo  School of Medicine, Hirosaki University Instructor, 医学部, 助手 (30003411)
KUSHIKATA Tetsuya  University Hospital, Hirosaki University Instructor, 医学部・附属病院, 助手 (80250603)
窪田 武  弘前大学, 医学部・附属病院, 医員
安沢 則之  弘前大学, 医学部・附属病院, 医員
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsGeneral anesthetic agents / Noradrenaline / Dopamine / Glutamate / Voltage sensitive Ca^<2+> channel / GABA_A receptor / Rats / Microdialysis / 神経伝達物質 / 静脈麻酔薬 / アセチルコリン受容体 / GABA受容体 / 大脳皮質 / 線条体 / チオペンタール / ペントバルビタール / フェノバルビタール / バルビツール酸 / バルビチュレート / カルシウムチャンネルブロッカー / ケタミン / プロポフォール
Research Abstract

[In Vitro] We used model of K^+-evoked neurotransmitter (noradrebaline [NA], dopamine and glutamate) release from rat brain slices to study effects of iv anesthetic agents on voltage sensitive Ca^<2+> channels (VSCCs). First, we found that the release is mediated mainly via P/Q-VSCCs. Second, iv anesthetic agents except ketamine significantly inhibit the release in a concentration dependent manner. Thus, these anesthetic agents may inhibit VSCC.However, bicuculline, a GABA_A receptor antagonist, reversed the inhibitory effects of iv anesthetic agents. Therefore, it is likely that activation of GABA_A receptors by these anesthetic agents may reduce VSCC activities.
[In Vivo] Using microdialysis method, we studied effects general anesthetic agents on NA release from several brain regions. We found that anesthetics inhibiting NMDA receptor increase NA release, whereas anesthetics activating GABA_A receptor reduce the release. Isoflurane that has both characters decreases the release in the cerebrocortex and increases in the preoptic area of anterior hypothalamus. As sleep-inducing NAergic neurons exist, increase in NA release by NMDA antagonist like anesthetics may contribute to activating sleep-inducing NAergic neurons. In contrast, decrease in NA release by GABA_A agonist like anesthetics may induces inhibition of wakefulness-inducing NAergic neurons.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kubota T, et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal cortex in rats"Canadian Journal of Anaesthesia. 46. 282-292 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota T, et al.: "Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats."Brain Research. 840. 175-178 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota T, et al.: "Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats. -GABA_A receptor activator vs NMDA receptor inhibitor-."Psychopharmacology. 146. 335-338 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota T, et al.: "Inhibitory effects of clonidine on ketamine-induced noradrenaline release from the medial prefrontal cortex in rats."British Journal of Anaesthesia. 83. 945-947 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 工藤美穂子 他: "バルビツレートのラット線条体切片からのドーパミンおよびノルアドレナリン放出に及ぼす影響."麻酔と蘇生. 34. 243-246 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kushikata T, et al.: "Isoflurane but not propofol anesthesia modulates norepinephrinergic neuronal activity in rat preoptic area ; a diversity of anesthetics effects on central nervous system."Progress in Anesthetic Mechanism. 6. 292-298 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirota K, et al.: "Inhibitory effects of barbiturates on K^+-evoked noradrenaline and dopamine release from rat striatal slices."Neuroscience Letters. 291. 175-178 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirota K, et al.: "Inhibitory effects of intravenous anaesthetic agents on K^+-evoked noradrenaline and dopamine release from rat striatal slices."British Journal of Anaesthesia. 85. 874-880 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota T, Anzawa N, Hirota K, et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal cortex in rats."Canadian Journal of Anaesthesia. 46. 388-92 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota K, Hirota K, Anzawa N, et al.: "Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats."Brain Research. 840. 175-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota K, Hirota K, Yoshida H, et al.: "Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats. -GABA_A receptor activator vs NMDA receptor inhibitor-."Psychopharmacology. 146. 335-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota K, Hirota K, Yoshida H, et al.: "Inhibitory effects of clonidine on ketamine-induced noradrenaline release from the medial prefrontal cortex in rats."British Journal of Anaesthesia. 83. 945-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kushikata T, Kubota T, Yoshida H, et al.: "Isoflurane but not propofol anesthesia modulates norepinephrinergic neuronal activity in rat preoptic area ; a diversity of anesthetics effects on central nervous system."Progress in Anesthetic Mechanism. 6. 292-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirota K, Kudo M, Kudo T, et al.: "Inhibitory effects of barbiturates on K^+-evoked noradrenaline and dopamine release from rat striatal slices."Neuroscience Letters. 291. 175-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirota K, Kudo M, Kudo T, Matsuki A, Lambert DG.: "Inhibitory effects of intravenous anaesthetic agents on K^+-evoked noradrenaline and dopamine release from rat striatal slices."British Journal of Anaesthesia. 85. 874-80 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kushikata T, et al.: "Isoflurane but not propofol anesthesia modulates norepinephrinergic neuronal activity in rat preoptic area ; a diversity of anesthetics effects on central nervous system."Progress in Anesthetic Mechanism. 6. 292-298 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirota K, et al.: "Inhibitory effects of barbiturates on K^+-evoked noradrenaline and dopamine release from rat striatal slices."Neuroscience Letters. 291. 175-178 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 工藤美穂子 他: "Nociceptin/Orphanin FQのラット大脳皮質切片からのグルタメート放出に及ぼす影響."麻酔と蘇生. 36. 9-10 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirota K, et al.: "Inhibitory effects of intravenous anaesthetic agents on K^+-evoked noradrenaline and dopamine release from rat striatal slices."British Journal of Anaesthesia. 85. 874-880 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubota T., Anzawa N., Hirota K. et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal contex in rats"Can J Anaesth. 46. 388-392 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota K., Hirota K., Yoshida H. et al.: "Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats. - GABA_A receptor activator vs NMDA receptor inhibitor -"Psychopharmacology. 146. 335-338 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota K., Hirota K., Anzawa N. et al.: "Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats"Brain Res. 840. 175-178 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 工藤美穂子、工藤剛、廣田和美、松木明知: "バルビツレートのラット線条体切片からのドーパミンおよびノルアドレナリン放出に及ぼす影響。"麻酔と蘇生. 34. 243-246 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota K., Hirota K., Yoshida H. et al.: "Inhibitory effects of clonidine on ketamine-induced noradrenaline release from the medial prefrontal cortex in rats"Br J Anaesth. 83. 945-947 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota T,Anzawa N,Hirota K,et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal cortex in rats." Canadian Journal of Anaesthesia. (in print.). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kudo M,Hirota K,et al: "Inhibitory effect of barbiturates on K^+-evoked noraddrenaline and dopamine releases from rat striatum slices." Anesthesiology. 89. A803 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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