Journal of molecular neuroscience : MN
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Endoplasmic reticulum (ER) stress may play a role in status epilepticus (SE). Sprague-Dawley rats were randomized into three groups: control (saline), SE (pentylenetetrazol), and dentate gyrus (DG), pretreated with 2-deoxy-D-glucose (2-DG). Expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor 2α (eIF2α), and protein kinase RNA-like ER kinase (PERK) were determined. ⋯ GRP messenger RNA expression levels and protein levels in SE group was significantly increased as compared to the control group (P < 0.0001) and significantly decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated PERK protein expression level in SE group was significantly increased as compared to the control group (P < 0.0001), and significantly decreased in DG group as compared to the SE group (P < 0.0001) at the time of 12 and 24 h. Our results suggest that brain injury from SE might involve ER stress via the pro-apoptotic PERK-eIF2α-CHOP signaling pathway.
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Recent studies showed that combination of mu opioid receptor (MOP) agonism and monoamine reuptake inhibition may improve the therapeutic effect of opioids by reducing requirement for MOP activation. Tapentadol, showing such a combined mechanism of action, exhibits delayed analgesic tolerance development compared to pure MOP agonists. Here we investigated how opioid receptors are regulated following different schedules (two ranges of concentrations for 24 and 48 h) of tapentadol exposure in vitro in SH-SY5Y cells. ⋯ Differently from DAMGO, tapentadol or morphine showed no effects on MOP internalization. This study suggests that tapentadol affects MOP and NOP gene expression and MOP internalization showing a pattern distinct from classical MOP agonists. Whether these differences can explain the improved therapeutic profile of tapentadol remains to be investigated.