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.

麻醉剂对离子通道的影响一直是多项研究的焦点。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 是麻醉剂的靶标。然而，关于麻醉剂对脊髓水平的 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广泛用于研究众多脑离子通道和 GPCR。在初级传入神经元上发现了大量类型，无论是在它们的中枢或外周过程上，还是在背根神经节 (DRG) 细胞的细胞体上，并且据报道存在几种 GPCR。因此，DRG已被用于伤害感受的研究。(1)我们研究了麻醉药对培养的DRG中P物质诱发的细胞内[Ca^<2+>]([Ca^<2+>]_i)增加的影响。细胞。 P物质诱导单个DRG细胞中[Ca 2+ ]_i 快速增加。挥发性麻醉剂氟烷抑制物质P引起的[Ca^2+]_i增加。(2)曲马多、代谢物M1和αxalone抑制表达M_3的非洲爪蟾卵母细胞中表达的电压依赖性Na通道。高浓度右美托咪定抑制表达M_3的爪蟾卵母细胞表达的电压依赖性Na通道。(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。此外，氯胺酮和戊巴比妥抑制表达M_3的非洲爪蟾卵母细胞中表达的P物质受体功能。(4)我们研究了麻醉剂对培养的DRG细胞中食欲素A和神经肽FF诱发的[Ca^2+]_i增加的影响。食欲素A和神经肽FF诱导单个DRG细胞中[Ca^2+]_i快速增加，表明这些受体存在于DRG中。我们目前的结果将有助于理解麻醉剂的机制。