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

本研究旨在探讨大鼠背根神经节（DRG）神经元P2 X受体表达模式与细胞类型的关系。我们用辣椒素敏感性鉴定了急性分离的成年大鼠DFG神经元的伤害感受细胞。在电压钳条件下，发现两种类型的ATP激活电流，一种具有快速脱敏，另一种具有缓慢脱敏。此外，细胞与快速而不是缓慢的脱敏反应辣椒素，表明有一个电流动力学和辣椒素敏感性之间的相互关系。两种类型的神经元均对ATP和α，β-亚甲基-ATP（α，βmeATP）有反应。快脱敏神经元产生α，βmeATP的半数激活浓度（EC_（50））（11 μM）低于慢脱敏神经元（63 μM），但Hill系数相似。苏拉明和磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸四钠（PPADS）可拮抗α，β-meATP诱导的两种神经元电流。在RNA水平，DRG的小细胞主要表达P2 X3的mRNA，而中等大小的细胞表达P2 X2和P2 X3的FNA。相反，这两种mRNA在DRG的大细胞中均未检测到。这些结果表明，辣椒素敏感的，小尺寸的DRG神经元主要表达同源的P2 X3亚基和辣椒素不敏感的，中等尺寸的DRG神经元表达与P2 X2和P2 X3的异源多聚体受体。

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.