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A neuropharmacological Research for the Function of ATP Receptors in the Nociception

ATP受体在伤害感受中的作用的神经药理学研究

基本信息

批准号：
08457416
负责人：
INOUE Kazuhide
金额：
$ 4.74万
依托单位：
NATIONAL INSTITUTE OF HEALTH SCIENCES
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457416/
关键词：
ATP RECEPTORS PAIN DORSAL ROOT GANGLION NEURON ELECTROPHYSIOLOGY INTRACELLULAR CALCIUM C-FIBER

项目摘要

The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of rat dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DFG neurons from adult rats type using capsaicin sensitivity. Two types of ATP-activated currents, one with fast, the other with slow desensitization, were found under voltage-clamp conditions. In addition, cells with fast but not slow desensitization responded to capsaicin, indicating that there was a mutual relevance between current kinetics and capsaicin-sensitivity. Both types of neurons were responsive to ATP and α,β-methylene-ATP (α,βmeATP). The concentration of α,βmeATP producing half-maximal activation (EC50) of neurons with fast desensitization was less (11 μM) than that of neurons with slow desensitization (63 μM) , while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS) antagonized α,βmeATP-induced currents in both types of neurons. At the RNA level, small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed FNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large cells of the DRG. These results suggested that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3.

本研究旨在阐明P2X受体表达模式与大鼠背根神经节（DRG）神经元细胞类型之间的关系。我们利用辣椒素敏感性鉴定了成年大鼠急性分离DFG神经元的伤害感受细胞。在电压箝位条件下，发现两种类型的atp激活电流，一种是快速脱敏，另一种是缓慢脱敏。此外，快速脱敏而非缓慢脱敏的细胞对辣椒素有反应，表明电流动力学与辣椒素敏感性之间存在相互相关性。两种神经元均对ATP和α，β-亚甲基ATP （α，β -肉ATP）有反应。快速脱敏神经元产生半最大激活（EC50）的α、β肉atp浓度（11 μM）低于缓慢脱敏神经元（63 μM）， Hill系数相似。苏拉明和吡哆醛-磷酸-6-偶氮苯基-2',4'-二磺酸四钠（PPADS）可拮抗α，β meatp诱导的两类神经元电流。在RNA水平上，DRG的小细胞主要表达P2X3的mrna，中等细胞主要表达P2X2和P2X3的FNAs。相比之下，在DRG的大细胞中未检测到这两种mrna。这些结果表明，辣椒素敏感的小尺寸DRG神经元主要表达同质P2X3亚基，而辣椒素不敏感的中等大小DRG神经元则表达带有P2X2和P2X3的异聚体受体。