Chronic exposure of sensory neurones to increased levels of nerve growth factor modulates CB1/TRPV1 receptor crosstalk
Chronic exposure of sensory neurones to increased levels of nerve growth factor modulates CB1/TRPV1 receptor crosstalk
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DOI：
10.1038/sj.bjp.0707411
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发表时间：
2007-10-01
影响因子：
7.3
通讯作者：
Ross, R. A.
中科院分区：
文献类型：
--
作者：
Evans, R. M.;Scott, R. H.;Ross, R. A.
背景：大麻素受体CB 1和TRPV 1均表达于培养的背根神经节神经元上，大麻素受体可激活这两种受体。神经生长因子（NGF）水平的增加与慢性疼痛状态有关。实验方法：本研究的目的是比较AEA对低浓度和高浓度NGF下CB 1受体信号传导和TRPV 1-CB 1串扰的影响，使用电压钳电生理学和Fura-2钙成像。与低浓度NGF（20 ng ml（-1））相比，慢性暴露于高浓度NGF（200 ng ml（-1））可使对AEA（1 μ M）产生内向电流的神经元比例从7%增加到29%。相反，AEA对电压门控钙电流的抑制在低NGF中没有显著差异（33 +/-9%，与高NGF 28 +/- 6%相比）。CB和TRPV 1受体之间的串扰通过暴露于高NGF来调制。在低NGF水平下，暴露于CB 1受体拮抗剂SR 141716 A（100 nM）可使AEA诱导[Ca 2 +]（i）增加的神经元百分比从10%增加至23%。在高NGF中，拮抗剂不会改变应答者的百分比（33 - 30%）。在低神经生长因子，暴露于CB受体激动剂，WIN 55（1 μ M）减少辣椒素介导的增加[Ca 2 +]（i）到28 +/- 8%的控制相比，增强到172 +/- 26%的控制观察到在高NGF.Conclusions和影响：我们得出结论，大麻素介导的TRPV 1受体激活的调制改变后，暴露于高神经生长因子。
Background: Anandamide (AEA) activates both cannabinoid CB1 and TRPV1 receptors, which are expressed on cultured dorsal root ganglion neurones. Increased levels of nerve growth factor (NGF) are associated with chronic pain states.Experimental approach: The aim of this study was to compare of the effects of AEA on CB1 receptor signalling and TRPV1-CB1 crosstalk in low and high concentrations of NGF, using voltage-clamp electrophysiology and Fura-2 calcium imaging.Key results: Chronic exposure to high NGF (200 ng ml(-1)) as compared to low NGF (20 ng ml(-1)) increases the proportion of neurones that exhibit an inward current in response to AEA (1 mu M), from 7 to 29%. In contrast, inhibition of voltage-gated calcium currents by AEA is not significantly different in low NGF (33 +/- 9%, compared to high NGF 28 +/- 6%). Crosstalk between CB and TRPV1 receptors is modulated by exposure to high NGF. In low NGF, exposure to the CB1 receptor antagonist, SR141716A, (100 nM) increases the percentage of neurones in which AEA elicits an increase in [Ca2+](i), from 10 to 23%. In high NGF, the antagonist does not alter the percentage of responders ( 33 to 30%). In low NGF, exposure to the CB receptor agonist, WIN55 (1 mu M) reduces capsaicin-mediated increases in [Ca2+](i) to 28 +/- 8% of control as compared to an enhancement to 172 +/- 26% of control observed in high NGF.Conclusions and implications: We conclude that cannabinoid-mediated modulation of TRPV1 receptor activation is altered after exposure to high NGF.