Ross R A, Coutts A A, McFarlane S M, Anavi-Goffer S, Irving A J, Pertwee R G, MacEwan D J, Scott R H
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Neuropharmacology. 2001;40(2):221-32. doi: 10.1016/s0028-3908(00)00135-0.
Cannabinoids modulate nociceptive processing in models of acute, inflammatory and neuropathic pain. We have investigated the location and function of cannabinoid receptors on cultured neonatal dorsal root ganglion (DRG) neurones and F-11 cells, a dorsal root ganglionxneuroblastoma hybridoma which displays several of the features of authentic DRG neurones. CB(1) receptor immunolabelling was observed on the cell bodies and as fine puncta on processes of both cultured DRG neurones and F-11 cells. Additionally, fluorescence-activated cell sorting (FACS) analysis provided evidence that both CB(1) and CB(2) receptors are expressed on populations of cells within the cultured DRG and F-11 cells. The cannabinoid receptor agonist (+)-WIN55212 (10 and 100 nM) inhibited the mean voltage-activated Ca(2+) current in DRG neurones by 21% and 30%, respectively. The isomer, (-)-WIN55212 (10 and 100 nM) produced significantly less inhibition of 6% and 10% respectively. The CB(1) selective receptor antagonist SR141716A (100 nM) enhanced the peak high voltage-activated Ca(2+) current by 24% and simultaneous application of SR141716A (100 nM) and (+)-WIN55212 (100 nM) resulted in a significant attenuation of the inhibition obtained with (+)-WIN55212 alone. These data give functional evidence for the hypothesis that the analgesic actions of cannabinoids may be mediated by presynaptic inhibition of transmitter release in sensory neurones.
大麻素在急性、炎症性和神经性疼痛模型中调节伤害性感受处理。我们研究了大麻素受体在培养的新生背根神经节（DRG）神经元和F-11细胞（一种显示出真实DRG神经元若干特征的背根神经节-神经母细胞瘤杂交瘤）上的定位和功能。在培养的DRG神经元和F-11细胞的细胞体以及突起上观察到CB(1)受体免疫标记，呈细点状。此外，荧光激活细胞分选（FACS）分析提供证据表明，CB(1)和CB(2)受体均在培养的DRG和F-11细胞内的细胞群体上表达。大麻素受体激动剂(+)-WIN55212（10和100 nM）分别使DRG神经元中平均电压激活的Ca(2+)电流抑制21%和30%。其异构体(-)-WIN55212（10和100 nM）的抑制作用明显较小，分别为6%和10%。CB(1)选择性受体拮抗剂SR141716A（100 nM）使峰值高电压激活的Ca(2+)电流增强24%，同时应用SR141716A（100 nM）和(+)-WIN55212（100 nM）导致单独使用(+)-WIN55212时获得的抑制作用显著减弱。这些数据为大麻素的镇痛作用可能由感觉神经元中递质释放的突触前抑制介导这一假说提供了功能证据。
