College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Neurochem Int. 2010 Mar;56(4):590-6. doi: 10.1016/j.neuint.2010.01.001. Epub 2010 Jan 11.
Although arachidonoyl ethanolamide (AEA or anandamide) is the first identified endocannabinoid, its roles in synaptic signaling and neuronal survival are still controversial. Here we report that AEA induced a dose-dependent elevation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) in mouse hippocampal neurons in culture. This potentiation was not blocked by SR141716 or AM251, selective cannabinoid receptor antagonists, indicating that the AEA elevation of mEPSCs is not mediated via the CB1 receptor. Similarly, capsazepine and iodoresiniferatoxin, selective vanilloid receptor antagonists, and ryanodine also failed to inhibit the effect of AEA on mEPSCs. However, 2-APB and Xestospongin C, IP3 inhibitors, significantly attenuated AEA-induced increase in hippocampal excitatory synaptic transmission. Application of 3-deoxy-3-fluoro-d-myo-inositol 1,4,5-trisphosphate enhanced the frequency of mEPSCs and occluded the effect of AEA on mEPSCs. Our results suggest that AEA-produced stimulatory effect on excitatory glutamatergic synaptic transmission is likely mediated via an IP3 pathway.
尽管花生四烯酰乙醇胺（AEA 或大麻素）是第一个被鉴定的内源性大麻素，但它在突触信号传递和神经元存活中的作用仍存在争议。在这里，我们报告说 AEA 可诱导培养的小鼠海马神经元中微小兴奋性突触后电流（mEPSC）频率的剂量依赖性升高。这种增强作用不受 SR141716 或 AM251（选择性大麻素受体拮抗剂）的阻断，表明 AEA 升高 mEPSC 不通过 CB1 受体介导。同样，辣椒素和碘代树脂毒素，选择性香草素受体拮抗剂，以及ryanodine 也未能抑制 AEA 对 mEPSC 的作用。然而，2-APB 和 Xestospongin C，IP3 抑制剂，显著减弱了 AEA 诱导的海马兴奋性突触传递的增加。3-脱氧-3-氟-d-肌醇 1,4,5-三磷酸的应用增强了 mEPSC 的频率，并阻断了 AEA 对 mEPSC 的作用。我们的结果表明，AEA 对兴奋性谷氨酸能突触传递的刺激作用可能通过 IP3 途径介导。
