Opiate Antagonist Prevents μ- and δ-Opiate Receptor Dimerization to Facilitate Ability of Agonist to Control Ethanol-altered Natural Killer Cell Functions and Mammary Tumor Growth

Abstract

Background: Chronic treatment with a -receptor antagonist increases the ␦ ability of the agonist to promote natural killer cell functions in alcohol-and non-alcohol-treated animals. Results: Opiate receptor antagonist reduces the receptor heterodimerization but increases ligand sensitivity. Conclusion: Receptor dimerization controls feedback interaction between -and ␦-opiate receptors. Significance: Studying opiate receptor feedback interaction will promote better opiate-based therapy for immune diseases.

Molecular Pharmacology of δ-Opioid Receptors

“…The homodimerization process is thought to involve the C-terminal tail of DOPr because a mutant-receptor bearing a 15-amino acid deletion in the C-terminal tail failed to dimerize and did not undergo agonist-induced internalization (Cvejic and Devi, 1997). The levels of DOPr homodimers were also shown to be increased by the selective blockage of MOPr in natural killer cells (Sarkar et al, 2012). Again, no specific functional role of the homodimer was revealed in these studies.…”

“…The latter effect was mediated by a decrease in the rate of dissociation of DOPr ligands (Gomes et al, , 2011. In natural killer cells, heterooligomerization was rather associated with a decrease in opioid binding (Sarkar et al, 2012).…”

“…The existence of DOPr homo-oligomers was subsequently confirmed using various techniques such as coimmunoprecipitation or BRET assays (Cvejic and Devi, 1997;McVey et al, 2001;Ramsay et al, 2002;Sarkar et al, 2012). A specific functional role for the homodimer has not as yet been established.…”

“…In intact tissue, the existence of the DOPr-MOPr hetero-oligomer was also shown using an antibody directed against this oligomer (Gupta et al, 2010). Interestingly, the abundance of the DOPr-MOPr hetero-oligomer is increased by chronic treatment with morphine in neurons (Gupta et al, 2010) and by ethanol in natural killer cells (Sarkar et al, 2012). The subcellular compartment where MOPr and DOPr associate with each other remains a matter of investigation.…”

Breaking Bread: the Functions of Social Eating

“…One possibility may be that family and friends provide support and assistance in time of need (Spence 1954;McCullogh and York Barton 1991;Grayson 1993), and hence allow one to feel more relaxed in stressful situations. However, there is also evidence that endorphins 'tune' the immune system (Sarkar et al 2012). If so, it is possible that eating together may have health and survival benefits both directly and, through bigger and better social networks, indirectly.…”