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| Content Provider | Springer Nature Link |
|---|---|
| Author | Donica, Courtney L. Ramirez, Vanessa I. Awwad, Hibah O. Zaveri, Nurulain T. Toll, Lawrence Standifer, Kelly M. |
| Copyright Year | 2011 |
| Abstract | Endogenous neuropeptide orphanin FQ/nociceptin (OFQ/N) and its receptor, nociceptin orphanin FQ peptide receptor (NOPr), play a modulatory role throughout the body including nociceptive sensitivity, motor function, spatial learning, and the immune system. NOPr is an inhibitory G protein coupled receptor (GPCR) that modulates expression and release of inflammatory mediators from immune cells and in the CNS. Inhibitory GPCRs have been shown to activate the immune and central nervous system regulator, nuclear factor kappa B (NFκB), whose family consists of several subunits. 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 transcriptional activation. For the first time, we show that OFQ/N increases the nuclear accumulation (1.9–2.8-fold) and the DNA binding of NFκB (2.9-fold) by 2 h as determined by immunoblotting and electromobility shift assay, respectively. OFQ/N induction of NFκB binding to DNA is protein kinase C-dependent and NOPr-specific. OFQ/N stimulated binding of both NFκB p50 and p65 subunits to their consensus binding site on DNA. OFQ/N also induces transcriptional activation of an NFκB reporter gene 2.2-fold by 2 h with an EC$_{50}$ of 6.3 nM. This activation of NFκB by OFQ/N suggests a likely mechanism for its modulation of the central nervous and immune systems. |
| Starting Page | 617 |
| Ending Page | 625 |
| Page Count | 9 |
| File Format | |
| ISSN | 15571890 |
| Journal | Journal of Neuroimmune Pharmacology |
| Volume Number | 6 |
| Issue Number | 4 |
| e-ISSN | 15571904 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2011-05-06 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | NOP receptor Orphanin FQ/nociceptin NFκB Immune Opioid Cytokine Virology Neurosciences Immunology Cell Biology Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Allergy Pharmacology Immunology |
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