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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一些研究的焦点。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是麻醉药的靶标。然而，麻醉药对脊髓水平gpcr、离子通道和配体门控离子通道的作用机制尚不清楚。非洲爪蟾卵母细胞表达系统已被广泛用于研究多种脑离子通道和gpcr。在初级传入神经元上发现了大量的类型，无论是在其中央或外周突起上，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，DRG已被用于伤害感觉的研究。(1)研究了麻醉药对p物质诱导的DRG细胞内[Ca^<2+>] （[Ca^<2+>]_i）升高的影响。P物质诱导单个DRG细胞[Ca^<2+>]_i快速升高。挥发性麻醉剂氟烷抑制物质p引起的[Ca^<2+>]_i的增加。(2)曲马多、代谢物M1和阿霉素抑制表达M_3的爪蟾卵母细胞中电压依赖性Na通道的表达。高浓度右美托咪定抑制表达M_3的爪蟾卵母细胞中电压依赖性Na通道的表达。(3)大多数挥发性麻醉剂抑制了爪蟾卵母细胞中表达M_3的P物质受体功能。此外，氯胺酮和戊巴比妥抑制了爪蟾卵母细胞中表达M_3的P物质受体功能。(4)研究了麻醉药对培养的DRG细胞食欲素A和神经肽ff诱发的[Ca^<2+>]_i升高的影响。Orexin A和神经肽FF诱导单个DRG细胞快速升高[Ca^<2+>]_i，提示这些受体存在于DRG中。我们目前的结果将有助于理解麻醉药的机制。