Evans R M, Scott R H, Ross R A
Medical Faculty, University of Calgary, Calgary, Canada.
Br J Pharmacol. 2007 Oct;152(3):404-13. doi: 10.1038/sj.bjp.0707411. Epub 2007 Aug 13.
Anandamide (AEA) activates both cannabinoid CB(1) 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.
The aim of this study was to compare of the effects of AEA on CB(1) receptor signalling and TRPV1-CB(1) crosstalk in low and high concentrations of NGF, using voltage-clamp electrophysiology and Fura-2 calcium imaging.
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 microM), 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 CB(1) receptor antagonist, SR141716A, (100 nM) increases the percentage of neurones in which AEA elicits an increase in Ca(2+), 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 microM) reduces capsaicin-mediated increases in Ca(2+) to 28+/-8% of control as compared to an enhancement to 172+/-26% of control observed in high NGF.
We conclude that cannabinoid-mediated modulation of TRPV1 receptor activation is altered after exposure to high NGF.
花生四烯乙醇胺（AEA）可激活大麻素CB(1)受体和瞬时受体电位香草酸亚型1（TRPV1）受体，这些受体在培养的背根神经节神经元上表达。神经生长因子（NGF）水平升高与慢性疼痛状态相关。
本研究的目的是使用电压钳电生理学和Fura-2钙成像技术，比较低浓度和高浓度NGF条件下AEA对CB(1)受体信号传导和TRPV1-CB(1)相互作用的影响。
与低浓度NGF（20 ng/ml）相比，长期暴露于高浓度NGF（200 ng/ml）会使对AEA（1 μM）产生内向电流的神经元比例从7%增加到29%。相反，低浓度NGF（33±9%）和高浓度NGF（28±6%）条件下，AEA对电压门控钙电流的抑制作用无显著差异。CB和TRPV1受体之间的相互作用受高浓度NGF暴露的调节。在低浓度NGF条件下，暴露于CB(1)受体拮抗剂SR141716A（100 nM）会使AEA引起细胞内钙离子浓度（[Ca(2+)]i）升高的神经元百分比从10%增加到23%。在高浓度NGF条件下，该拮抗剂不会改变反应神经元的百分比（33%至30%）。在低浓度NGF条件下，暴露于CB受体激动剂WIN55（1 μM）会使辣椒素介导的[Ca(2+)]i增加降低至对照的28±8%，而在高浓度NGF条件下则增强至对照的172±26%。
我们得出结论，暴露于高浓度NGF后，大麻素介导的TRPV1受体激活调节发生改变。
