Exogenous nerve growth factor attenuates opioid-induced inhibition of voltage-activated Ba2+ currents in rat sensory neurons.
Exogenous nerve growth factor attenuates opioid-induced inhibition of voltage-activated Ba2+ currents in rat sensory neurons.
复制标题
外源性神经生长因子减弱阿片类药物诱导的大鼠感觉神经元电压激活 Ba2 电流的抑制。
DOI：
10.1016/j.neuroscience.2004.03.009
复制
发表时间：
2004
期刊：
影响因子：
3.3
通讯作者：
McDowell,TS
中科院分区：
文献类型：
--
作者：
McDowell,TS
神经生长因子（NGF）促进胚胎感觉神经元的存活，并在生后维持初级伤害感受神经元的表型特征。在炎性疼痛状态期间，NGF也有助于伤害感受器激活和痛觉过敏。本研究的目的是确定是否有一个额外的神经生长因子可能通过干扰阿片类药物介导的镇痛在初级伤害性神经元的原伤害性作用。感觉神经元从断乳大鼠的背根神经节分离，并保持在标准培养条件下，有或没有外源性NGF（50 ng/ml）。采用全细胞膜片钳技术，以Ba ~（2+）为电荷载体（IBa），记录单个神经元通过电压门控钙通道的电流。μ-阿片激动剂芬太尼（1 μM）和GABA激动剂巴氯芬（50 μM）用于测试IBa的G蛋白依赖性抑制。芬太尼对IBaby的抑制率为38±4%，而对NGF处理的IBaby的抑制率为25±2%（P<0.01）。NGF对IBacurrent幅度或动力学没有影响。早在暴露后4小时就观察到了NGF诱导的阿片类药物作用的衰减，但当通过浴灌注应用NGF长达40分钟时没有观察到，这表明该作用不是由快速磷酸化事件介导的。NGF的作用被TrkA自磷酸化的抑制剂K-252 a（100 nM）阻止。另一方面，Bacterium诱导的IBa抑制不受NGF治疗的影响，表明阿片类药物介导的抑制的NGF调制发生在G蛋白的上游。GTP-γ-S是一种非激动剂依赖的G蛋白激活剂，在未经处理的细胞和经NGF处理的细胞中，对IBA的抑制作用相似。结果表明，NGF选择性地减弱阿片介导的IBavia TrkA受体激活抑制，可能是通过改变阿片受体功能。
Nerve growth factor (NGF) promotes the survival of embryonic sensory neurons and maintains the phenotypic characteristics of primary nociceptive neurons postnatally. NGF also contributes to nociceptor activation and hyperalgesia during inflammatory pain states. The purpose of this study was to determine whether NGF might have an additional pronociceptive action by interfering with opioid-mediated analgesia in primary nociceptive neurons. Sensory neurons were isolated from the dorsal root ganglia of weanling rats and kept in standard culture conditions either with or without exogenous NGF (50 ng/ml). Currents through voltage-gated calcium channels were recorded from individual neurons using the whole cell patch clamp technique with Ba2+as the charge carrier (IBa). The μ-opioid agonist fentanyl (1 μM) and the GABABagonist baclofen (50 μM) were used to test G protein-dependent inhibition of IBa. Fentanyl inhibited IBaby an average of 38±4% in untreated cells vs. 25±2% in NGF-treated cells (P<0.01). NGF had no effect on IBacurrent magnitude or kinetics. The NGF-induced attenuation of opioid action was observed as early as 4 h after exposure, but was not seen when NGF was applied by bath perfusion for up to 40 min, suggesting that the effect was not mediated by a rapid phosphorylation event. The effect of NGF was prevented by K-252a (100 nM), an inhibitor of TrkA autophosphorylation. Baclofen-induced inhibition of IBa, on the other hand, was not affected by NGF treatment, suggesting that NGF modulation of opioid-mediated inhibition occurred upstream from the G protein. This was supported by the finding that GTP-γ-S, an agonist independent G protein activator, inhibited IBasimilarly in both untreated and NGF treated cells. The results show that NGF selectively attenuated opioid-mediated inhibition of IBavia TrkA receptor activation, possibly by altering opioid receptor function.