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

Abstract

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, NFκB. The NFκB family consists of several subunits, including p105 and p50. When activated, NFκB translocates to the nucleus and can modify transcription. To determine if OFQ/N modulates NFκB 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 NFκB at 30 min and increases the DNA binding of NFκB by 1 hr as determined by electromobility shift assay (EMSA). Additionally, immunoblot analysis of SH‐SY5Y cell lysates indicates that NFκB p50 protein expression is up‐regulated by 2 hr. This suggests that OFQ/N may modulate immune system function by activating NFκB. These studies were supported by DA017380 and OCAST grant HR08‐152 to KMS.