Orphanin FQ/Nociceptin Activates Nuclear Factor Kappa B In Neuronal Cells

Endogenous neuropeptide orphanin FQ/nociceptin (OFQ/N) and its receptor, opioid receptor like‐1 (ORL1; or Nociceptin orphanin peptide receptor, NOP), have been shown to play a modulatory role throughout the body on nociceptive sensitivity, including motor function, spatial learning, smooth muscle tone, cardiac function and the immune system. ORL1 is a G protein coupled receptor (GPCR) that couples to Gi/o proteins and modulates expression and release of inflammatory mediators from immune cells and in the CNS. Inhibitory GPCRs have been shown to activate the immune system regulator, NF κ B. The NF κ B family consists of several subunits, including p105 and p50. When activated, NF κ B translocates to the nucleus and can modify transcription. To determine if OFQ/N modulates NF κ B activity, SH‐SY5Y human neuroblastoma cells were treated with OFQ/N and assessed for changes in nuclear accumulation, DNA binding and protein expression. OFQ/N increases the nuclear accumulation of NF κ B at 30 min and increases the DNA binding of NF κ B by 1 hr as determined by electromobility shift assay (EMSA). Additionally, immunoblot analysis of SH‐SY5Y cell lysates indicates that NF κ B p50 protein expression is up‐regulated by 2 hr. This suggests that OFQ/N may modulate immune system function by activating NF κ B. These studies were supported by DA017380 and OCAST grant HR08‐152 to KMS.