2007 Fiscal Year Final Research Report Summary
The role of the metabotropic gultamete receptor in the pain mechanism
| Project/Area Number |
17591657
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
SHIGA Yousuke University of Occupational and Environmental Health, Japan, School of medicine, researcher (10399199)
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| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Pain mechanism / G protein couples receptors / Dorsal root ganglia cells / Metabotropic glutamte receptors / Anesthetics / Xenopus oocytes expression systems / Dexmedetomidine / Phosphorylation |
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| 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
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