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The study of antinociceptive effects of anesthetics and analgesics using dorsal root ganglia cells.

使用背根神经节细胞研究麻醉剂和镇痛剂的抗伤害作用。

基本信息

批准号：
15390479
负责人：
SHIGEMATSU Akio
金额：
$ 9.34万
依托单位：
University of Occupational Environmental Health(UOEH)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The effects of anesthetics on ion channels have been the focus of several studies. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein coupled receptor (GPCR) signaling. Further studies have shown that GPCRs are targets for anesthetics. However, less is known about the mechanisms of action of anesthetics on GPCRs, ion channels and ligand-gated ion channels in spinal cords levels. The Xenopus oocyte expression system has been used widely to study numerous brain ion channels and GPCRs. A large number of types have been found on primary afferent neurons, either on their central or peripheral processes or on the cell bodies of the dorsal root ganglion (DRG) cells and it is have been reported the presence of several GPCRs. Therefore the DRG have been used for the study of nociception.(1)We studied the effects of anesthetics on substance P-evoked intracellular [Ca^<2+>] ([Ca^<2+>]_i)increasing in cultured DRG cells. Substance P induced a rapid [Ca^<2+>]_i increase in single DRG cell. Volatile anesthetics halothane inhibited the substance P-evoked increases in [Ca^<2+>]_i.(2)Tramadol, metabolite M1 and alphaxalone inhibited voltage dependent Na channels expressed in Xenopus oocytes that expressed M_3. High concentration of dexmedetomidine inhibited voltage dependent Na channels expressed in Xenopus oocytes that expressed M_3.(3)Most volatile anesthetics inhibited substance P receptor function expressed in Xenopus oocytes that expressed M_3. Moreover, ketamine and pentobarbital inhibited substance P receptor function expressed in Xenopus oocytes that expressed M_3.(4)We studied the effects of anesthetics on orexin A and neuropeptide FF-evoked [Ca^<2+>]_i increasing in cultured DRG cells. Orexin A and neuropeptide FF induced a rapid [Ca^<2+>]_i increase in single DRG cell suggesting that these receptors exist in DRG.Our present results would be useful for understanding the mechanisms of anesthetics.

麻醉药对离子通道的影响一直是研究的热点。在过去的十年中，我们对G蛋白偶联受体（GPCR）信号传导的生理学和药理学的理解取得了重大进展。进一步的研究表明，GPCR是麻醉剂的靶点。然而，关于麻醉剂在脊髓水平上对GPCR、离子通道和配体门控离子通道的作用机制知之甚少。非洲爪蟾卵母细胞表达系统已被广泛用于研究脑离子通道和GPCR。已经在初级传入神经元上发现了大量的类型，无论是在它们的中央或外周突起上，还是在背根神经节（DRG）细胞的细胞体上，并且已经报道了几种GPCR的存在。因此，背根神经节已被用于伤害性感受的研究。(1)We研究麻醉药对P物质诱发的DRG细胞内[Ca^<2+>]（[Ca^<2+]_i）升高的影响。P物质引起单个DRG细胞[Ca^<2+>] i迅速升高。挥发性麻醉药氟烷可抑制P物质诱发的[Ca^<2+>]_i升高。（2）曲马多、代谢产物M1和阿法沙龙抑制表达M3的非洲爪蟾卵母细胞电压依赖性钠通道的表达。高浓度右美托咪定抑制表达M_3的非洲爪蟾卵母细胞电压依赖性钠通道的表达。（3）大多数挥发性麻醉药抑制表达M_3的爪蟾卵母细胞表达的P物质受体功能。氯胺酮和戊巴比妥抑制表达M_3的非洲爪蟾卵母细胞表达的P物质受体功能。(4)We研究麻醉药对食欲素A和神经肽FF引起的DRG细胞[Ca^<2+>]_i升高的影响。Orexin A和神经肽FF可诱导单个DRG细胞内[Ca^<2+>] i迅速升高，提示它们可能存在于DRG内，本实验结果为进一步了解麻醉药的作用机制提供了依据。