| Co-Investigator(Kenkyū-buntansha) |
SHIRAISHI Munehiro University of Occupational and Environmental Health, School of Medicine, Instructor (40389458)
UEZONO Yasuhito Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor (20213340)
UETA Yoichi University of Occupational and Environmental Health, School of Medicine, Professor (10232745)
松井 稔 東京大学, 医科学研究所, 助手 (50282611)
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| Budget Amount *help |
¥3,670,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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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-HT_2 and orexin receptors. Consequently, the DRG has been used to study nociception. It is 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. We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on SP-induced currents mediated by SPR expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the volatile anesthetics tested, and ethanol, inhibited SPR-induced Ca(2+
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)-activated Cl(-) currents at pharmacologically relevant concentrations. Neurosteroid, alphaxalone, inhibited the acetylcholine (Ach)-mediated responses of M(1) and M(3) receptors expressed in Xenopus oocytes, whereas DHEA did not. Moreover, we examined the the effects of Dexmedetomidine in this systems. Dexmedetomidine did not affect the 5-HT_2c-, 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 C1^- currents in Xenopus oocytes expressing M_1 receptors. In contrast, dexmedetomidine inhibited the Ach-induced currents in Xenopus oocytes expressing M_3 receptors. Dexmedetomidine reduced the Ach-induced C1^- currents after treatment with the selective protein kinase C inhibitor GF109203X. Moreover, the compound inhibited the muscarinic receptor-mediated increases in [Ca^<2+>; 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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