Kong L Y, Jeohn G, Hudson P M, Du L, Liu B, Hong J S
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
J Biomed Sci. 2000 May-Jun;7(3):241-7. doi: 10.1007/BF02255472.
Previously we reported that ultralow concentrations of dynorphins (10(-16) to 10(-12) M) inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and proinflammatory cytokines in mouse glia without the participation of kappa-opioid receptors. In the current study using mouse cortical neuron-glia cocultures, we examined the possibility that inhibition of glia inflammatory response by dynorphins might be neuroprotective for neurons. LPS, in a concentration-dependent manner, markedly increased the release of lactate dehydrogenase (LDH), an indicator of cellular injury. Ultralow concentrations (10(-14) to 10(-12) M) of dynorphin (dyn) A-(1-8) significantly prevented the LPS-induced release of LDH, loss of neurons, and changes in cell morphology, in addition to inhibition of LPS-induced nitrite production. Meanwhile, ultralow concentrations (10(-15) to 10(-13) M) of des-[Tyr(1)]-dyn A-(2-17), a nonopioid peptide which does not bind to kappa-opioid receptors, exhibited the same inhibitory effect as dyn A-(1-17). These results suggest that dynorphins at ultralow concentrations are capable of reducing LPS-induced neuronal injury and these neuroprotective effects of dynorphins are not mediated by classical opioid receptors.
此前我们报道，超低浓度的强啡肽（10^(-16)至10^(-12) M）在无κ-阿片受体参与的情况下，可抑制小鼠神经胶质细胞中脂多糖（LPS）诱导的一氧化氮（NO）生成及促炎细胞因子产生。在当前使用小鼠皮质神经元-神经胶质细胞共培养物的研究中，我们探究了强啡肽对神经胶质细胞炎症反应的抑制作用可能对神经元具有神经保护作用的可能性。LPS以浓度依赖的方式显著增加了乳酸脱氢酶（LDH）的释放，LDH是细胞损伤的一个指标。超低浓度（10^(-14)至10^(-12) M）的强啡肽A-(1-8)除了抑制LPS诱导的亚硝酸盐生成外，还显著阻止了LPS诱导的LDH释放、神经元丢失及细胞形态变化。同时，超低浓度（10^(-15)至10^(-13) M）的去-[酪氨酸(1)]-强啡肽A-(2-17)，一种不与κ-阿片受体结合的非阿片肽，表现出与强啡肽A-(1-17)相同的抑制作用。这些结果表明，超低浓度的强啡肽能够减轻LPS诱导的神经元损伤，且强啡肽的这些神经保护作用不是由经典阿片受体介导的。
