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

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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.