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2007 Fiscal Year Final Research Report Summary

The role of the metabotropic gultamete receptor in the pain mechanism

Research Project

Project/Area Number 17591657
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

SHIGA Yousuke  University of Occupational and Environmental Health, Japan, School of medicine, researcher (10399199)

Co-Investigator(Kenkyū-buntansha) MINAMI Koichiro  Jichi Medical University, School of medicine, assistant professor (70279347)
SHIRAISHI Munehiro  University of Occupational&Environmental Health(UOEH), School of medicine, researcher (40389458)
UEZONO Yasuhito  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor (20213340)
Project Period (FY) 2005 – 2007
KeywordsPain mechanism / G protein couples receptors / Dorsal root ganglia cells / Metabotropic glutamte receptors / Anesthetics / Xenopus oocytes expression systems / Dexmedetomidine / Phosphorylation
Research Abstract

The dorsal root ganglion (DRG) neurons and associated primary afferent nerves transmit different sensory modalities, including nociception, to the spinal dorsal horn. Many types of neuronal cell have been found on primary afferent neurons, either on their central or peripheral processes or on the cell bodies of DRG cells and the presence of several GPCRs has been reported, including substance P, muscarinic, 5 HT2 and orexin receptors. Consequently, the DRG has been used to study nociception.
The metabotropic glutamate receptors (mGluRs) show little sequence homology with most other metabotropic receptors and are important modulators of synaptic transmission in the mammalian central nervous system. It was of interest to determine drug actions on these receptors, and we investigated the role of the glutamate receptor in DRG and the effects of anesthetics on the function of mGluR1 and mGluR5 expressed in Xenopus laevis oocytes.
In the projects, we found the glutamate-evoked increase in Ca^< … More 2+>i in cultured DRG cells that show the presence of the glutamate receptors.
In the experiment using Xenopus oocytes systems, anesthetics inhibited mGluR5-induced Ca^<2+>-dependent currents, yet pharmacologically relevant concentrations of these compounds had little effect on the glutamate-induced currents in the oocytes expressing mGluR 1.
Moreover, we examined the the effects of Dexmedetomidine in this systems. Dexmedetomidine did not affect the 5 HT2C-, substance P-, or orexin A-induced Cl- currents in oocytes expressing the respective receptors. The compound also had little effect on the acetylcholine (ACh, 1μM)-induced Ca^<2+>-activated Cl- currents in Xenopus oocytes expressing M_1 receptors. In contrast, dexmedetomicline inhibited the ACh-induced currents in Xenopus oocytes expressing M_3 receptors. Moreover, the compound inhibited the muscarinic receptor-mediated increases in Ca^<2+>i in cultured DRG cells in a concentration-dependent manner.
From these results, the glutamate receptors may play the important role in pain transmission in DRG. Less

  • Research Products

    (6 results)

All 2007

All Journal Article (6 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Pharmacological aspects of the effects of tramadol on G-protein coupled receptors2007

    • Author(s)
      Minami K., et. al.
    • Journal Title

      J Pharmacol Sci. 103

      Pages: 253-260

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Dexmedetomidine inhibits muscarinic type 3 receptors expressed in Xenopus oocytes and muscarine-induced intracellular Ca^<2+> elevation in cultured rat dorsal root ganglia cells2007

    • Author(s)
      Takizuka A., et. al.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol. 375

      Pages: 293-301

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Effects of anesthetics on the function of orexin-1 receptors expressed in Xenopus oocytes2007

    • Author(s)
      Minami K., et. al.
    • Journal Title

      Pharmacology 79

      Pages: 236-242

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Pharmacological aspects of the effects of tramadol on Gprotein coupled receptors.2007

    • Author(s)
      Minami K, Uezono Y, Ueta Y.
    • Journal Title

      J Pharmacol Sci. 103(3)

      Pages: 253-60

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dexmedetomidine inhibits muscarinic type 3 receptors expressed in Xenop us oocytes and muscarine induced intracellular Ca^<2+> elevation in cultured rat dorsal root ganglia cells.2007

    • Author(s)
      Takizuka A, Minami K, Uezono Y, Horishita T, Yokoyama T, Shiraishi M, Sakurai T, Shigematsu A, Ueta Y.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol. 375(5)

      Pages: 293-301

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of anesthetics on the function of orexiir 1 receptors expressed in Xen op us oocytes.2007

    • Author(s)
      Minami K, Uezono Y, Sakurai T, Horishita T, Shiraishi M, Ueta Y.
    • Journal Title

      Pharmacology. 79(4)

      Pages: 236-42

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

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Published: 2010-02-04  

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