摘要
目的探讨地塞米松对大鼠背根神经节（DRG）神经元ATP激活电流的快速调节作用及其相关信号机制。方法采用酶加机械法分离、培养大鼠DRG神经元,全细胞膜片钳法记录ATP激活电流及地塞米松对ATP激活电流的影响。结果细胞外给予ATP（100μmol/L）在大鼠DRG神经元可引起3种内向电流,即快速脱敏感反应电流（快反应电流）、慢速脱敏感反应电流（慢反应电流）及混合电流。预先给予地塞米松（0.01~10μmol/L）可剂量依赖性地抑制ATP快反应电流及混合电流中的快反应电流成分,而对慢反应电流及混合电流中的慢反应电流成分无明显影响。地塞米松对ATP激活电流的快速抑制作用可被糖皮质激素受体拮抗剂RU38486（10μmol/L）、蛋白激酶A抑制剂H-89（10μmol/L）阻断,而G蛋白激活抑制剂GDP-β-S（0.2mmol/L）、蛋白激酶C抑制剂Chelerythrine chloride（10μmol/L）对地塞米松的快速抑制作用无明显影响。结论地塞米松通过糖皮质激素受体激活细胞内PKA信号途径可选择性地抑制大鼠DRG神经元中由P2X3受体介导的ATP快反应电流,提示糖皮质激素可能通过非基因组作用影响初级感觉神经元的ATP/P2X3受体功能而参与痛觉的调制。
Objective Glucocorticoid hormone may nongenomically affect cell functions in addition to its classic effects on gene expression. The purpose of present study was to explore whether dexamethasone, a synthetical glucocorticoid hormone, has a rapid nongenomic effect on ATP-induced currents in rat dorsal root ganglion （DRG） neurons and the related signal transduction pathway. Methods The effects of dexamethasone on ATP-induced currents were studied on cultured DRG neurons using patch clamp technique. Results Three types of currents （transient, sustained and biphasic） were evoked by ATP （100 μmol/L） in cultured DRG neurons. When DRG neurons were pretreated with dexamethasone （0.01-10μmol/L） for 30s, inhibition of the transient current and the transient component of the biphasic current evoked by ATP in DRG neurons was observed. The inhibitory effect of dexamethasone was dose-dependent. However, dexamethasone did not seem to affect the sustained current and the sustained component of the biphasic current induced by ATP. The inhibitory effect of dexamethasone on ATP-induced currents was blocked by glucocorticoid receptor antagonist RU38486 （10μmol/L） and protein kinase A inhibitor H-89 （10μmol/L）, but not by G protein inhibitor GDP-β-S （0.2mmol/L） and protein kinase C inhibitor chelerythrine chloride （10μmol/L）. Conclusions Dexamethasone can selectively inhibit the transient current mediated by P2X3 receptors in DRG neurons. The inhibitory effect of dexamethasone might be mediated by glucocorticoid receptor through activating PKA signal pathway. These results suggest that glucocorticoid hormone might participate in the control of pain by modulating the actions of extracellular ATP in sensory neurons.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2008年第5期590-592,共3页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金资助课题30672022
关键词
地塞米松
神经节
脊
腺苷三磷酸
膜片钳术
dexamethasone
ganglia, spinal
adenosine triphosphate
patch-clamp techniques
