Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna, 40126, Italy.
J Mol Neurosci. 2012 Feb;46(2):285-92. doi: 10.1007/s12031-011-9552-0. Epub 2011 May 21.
Several studies demonstrated a cross-talk between the opioid and cannabinoid system. The NOP receptor and its endogenous ligand nociceptin/orphanin FQ represent an opioid-related functional entity that mediates some non-classical opioid effects. The relationship between cannabinoid and nociceptin/NOP system is yet poorly explored. In this study, we used the neuroblastoma SH-SY5Y cell line to investigate the effect of delta-9-tetrahydrocannabinol (∆(9)-THC) on nociceptin/NOP system. Results revealed that the exposure to ∆(9)-THC (100, 150, and 200 nM) for 24 h produces a dose-dependent NOP receptor B (max) down-regulation. Moreover, ∆(9)-THC caused a dose-dependent decrease in NOP mRNA levels. The selective cannabinoid receptor CB1 antagonist AM251 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide) reduces both effects, suggesting that ∆(9)-THC activation of CB1 receptor is involved in the observed effects. These data show evidence of a cross-talk between NOP and CB1 receptors, thus suggesting a possible interplay between cannabinoid and nociceptin/NOP system.
几项研究表明阿片类和大麻素系统之间存在串扰。NOP 受体及其内源性配体孤啡肽/孤啡肽 FQ 代表一种与阿片类相关的功能实体，介导一些非经典阿片类效应。大麻素和孤啡肽/NOP 系统之间的关系尚未得到充分探索。在这项研究中，我们使用神经母细胞瘤 SH-SY5Y 细胞系来研究 delta-9-四氢大麻酚（∆(9)-THC）对孤啡肽/NOP 系统的影响。结果表明，暴露于 ∆(9)-THC（100、150 和 200 nM）24 小时会导致 NOP 受体 B（max）呈剂量依赖性下调。此外，∆(9)-THC 导致 NOP mRNA 水平呈剂量依赖性下降。选择性大麻素受体 CB1 拮抗剂 AM251（1-(2,4-二氯苯基)-5-(4-碘苯基)-4-甲基-N-1-哌啶基-1H-吡唑-3-甲酰胺）减少了这两种作用，表明 ∆(9)-THC 激活 CB1 受体参与了观察到的作用。这些数据表明 NOP 和 CB1 受体之间存在串扰，因此表明大麻素和孤啡肽/NOP 系统之间可能存在相互作用。
