The Inhibitory Effects of Intravenous Anesthetics on Substance P Receptor in U373 MG Human Astrocytoma Cells.

神经肽P物质(SP)是中枢和外周神经系统神经源性炎症的重要介质。我们研究了氯胺酮对高表达SPR的人星形细胞瘤细胞系U373 MG细胞中核因子B的磷酸化以及丝裂原活化蛋白激酶(MAPK)激活的影响。免疫印迹法检测磷酸化的NF-kB和MAPK(ERK1/2、P-38、JNK)的表达水平。SP可促进U373 MG细胞中NF-kB和MAPKs的磷酸化及IL-6和IL-8的产生。氯胺酮可减弱U373 MG细胞中NF-kB p65和MAPKs的磷酸化。氯胺酮可抑制IL-6和IL-8的产生。氯胺酮对SP诱导的细胞因子产生的抑制作用可能是通过激活核因子-kB抑制MAPKs而实现的。这一发现提示，这些化合物对SPR功能的抑制可能在氯胺酮的镇痛作用中起重要作用。

The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous system. We investigated the effects of ketamine on NF-B phosphorylation, as well as the activation of the mitogen-activated protein kinase (MAPK) in the human astrocytoma cell line U373 MG cells which express high levels of SPR. The level of phosphorylated NF-kB and MAPK (ERK1/2, P-38, and JNK) were detected by western blotting. SP increased the phosphorylation of NF-kB and MAPKs and production of IL-6 and 8. Ketamine attenuated the phosphorylation of NF-kB p65 and MAPKs in U373 MG cells. Production of IL-6 and 8 were suppressed by ketamine. The inhibitory effects of ketamine on SP-induced cytokine production may be mediated by suppressing MAPKs via NF-kB activation. This finding suggests that the inhibition of SPR function by these compounds may be important in the analgesic effects of ketamine.