Role of Docosahexaenoic Acid in Mu Opioid Receptor Phosphorylation and Desensitization

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIAAA	SIG-1

Authors

• M Akbar
• H.Y. Kim

Abstract

Previous studies have demonstrated the role of Mu opioid receptor (MOR) in opiates addiction, tolerance and in pain management. We have shown that omega-3 fatty acid, particularly docosahexaenoic acid (DHA) exerts protective effects in neuronal cells, through accumulation of phosphatidylserine (PS) and thereby modulating protein kinases. In this study, we investigated the effects of DHA-induced membrane modification on MOR signaling. A permanent clone expressing hMOR was prepared using Neuro 2A cells. Subsequently, cells were enriched with DHA that accumulates PS in the plasma membrane, and MOR phosphorylation was evaluated in comparison to oleic acid (OA) and docosapentaenoic acid (DPAn-6). We found that, enrichment of cells with DHA, but to a lesser extent OA and DPA, potentiated DAMGO-induced MOR phosphorylation and internalization. However, radio-ligand binding to MOR did not show significant differences. This modulation of phosphorylation is possibly due to changes in receptor conformation away from the ligand binding domain or GRK activation that requires membrane translocation. Altered phosphorylation, internalization and resensitization of MOR due to structural modification of neuronal membranes may have significant implication in addiction processes.

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