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Nerve growth factor,sphingomyelins,and sensitization in sensory neurons

Nerve growth factor,sphingomyelins,and sensitization in sensory neurons
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摘要 Because nerve growth factor(NGF)is elevated during inflammation,plays a causal role in the initiation of Because nerve growth factor (NGF) is elevated during inflammation, plays a causal role in the initiation of hyperalgesia, and is known to activate the sphingomyelin signalling pathway, we examined whether NGF and its putative second messenger, ceramide, could modulate the excitability of capsaicin-sensitive adult sensory neurons. Using the whole-cell patch-clamp recording technique, exposure of isolated sensory neurons to either 100 ng/mL NGF or I mmol/L N-acetyl sphingosine (C2-ceramide) produced a 3-4 fold increase in the number of action potentials (APs) evoked by a ramp of depolarizing current in a time-dependent manner. Intracellular perfusion with bacterial sphingomyelinase (SMase) also increased the number of APs suggesting that the release of native ceramide enhanced neuronal excitability. Glutathione, an inhibitor of neutral SMase, completely blocked the NGF-induced augmentation of AP firing, whereas dithiothreitol, an in- hibitor of acidic SMase, was without effect. In the presence of glutathione and NGF, exogenous ceramide still enhanced the number of evoked APs, indicating that the sensitizing action of ceramide was downstream of NGF. To investigate the mechanisms of actions for NGF and ceramide, isolated membrane currents were examined.
作者 Grant D.Nicol
出处 《生理学报》 CAS CSCD 北大核心 2008年第5期603-604,共2页 Acta Physiologica Sinica
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参考文献4

  • 1Zhang YH, Vasko MR, Nicol GD. Ceramide, a putative second messenger for nerve growth factor, modulates the TTX-resistant Na^+ current and delayed rectifier K^+ current in rat sensory neurons. J Physiol 2002; 544: 385-402.
  • 2Zhang YH, Nicol GD. NGF-mediated sensitization of the excitability of rat sensory neurons is prevented by a blocking antibody to the p75 neurotrophin receptor. Neurosci Lett 2004;366:187-192.
  • 3Zhang YH, Vasko MR, Nicol GD. Intracellular sphingosine 1- phosphate mediates the increased excitability produced by nerve growth factor in rat sensory neurons. J Physio12006; 575: 101- 113.
  • 4Zhang YH, Fehrenbacher JC, Vasko MR, Nicol GD. Sphingosine-1-phosphate via activation of a G-protein-coupled receptor(s) enhances the excitability of rat sensory neurons. J Neurophysiol 2006; 96:1042-1052.

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