| Title: |
Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities. |
| Authors: |
Fujita, Wakako1, Gomes, Ivone1, Devi, Lakshmi A1 |
| Source: |
British Journal of Pharmacology. Jan2015, Vol. 172 Issue 2, p375-387. 13p. |
| Subject Terms: |
*OPIOID receptors, *PHARMACOLOGY, *CELLULAR signal transduction, *G protein coupled receptors, *LIGANDS (Biochemistry), *PHARMACEUTICAL research |
| Abstract: |
Several studies suggest that heteromerization between μ ( MOP) and δ ( DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β-arrestin-mediated signalling in the context of the MOP-D OP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-D OP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identification of a MOP-D OP receptor heteromer-biased agonist that activates both G protein-mediated and β-arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-D OP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize findings regarding the biological and functional characteristics of the MOP-D OP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands. Linked Articles This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit [ABSTRACT FROM AUTHOR] |
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