G protein-coupled receptors can interact with each other to form homomers or heteromers. Homomers involve interactions with the same receptor type while heteromers involve interactions between two different GPCRs. These receptor-receptor interactions modulate not only the binding but also the signaling and trafficking properties of individual receptors. Opioid receptor heteromerization has been extensively investigated with the objective of identifying novel therapeutic targets that are as potent as morphine but without the side effects associated with chronic morphine use. In this context studies have described heteromerization between the different types of opioid receptors and between opioid receptors and a wide range of GPCRs including adrenergic, cannabinoid, catecholamine, metabotropic glutamate and sensory neuron specific receptors. Recent advances in the field involving the generation of heteromer specific reagents (antibodies or ligands) or of membrane permeable peptides that disrupt the heteromer interaction are helping to elucidate the physiological role of opioid receptor heteromers and the contribution of the partner receptor to the side-effects associated with opioid use. For example studies using membrane permeable peptides targeting the heteromer interface have implicated μ and δ receptor heteromers in the development of tolerance to morphine and μ and gastrin-releasing peptide receptor heteromers in morphine-induced itch. In addition, a number of ligands that selectively target opioid receptor heteromers exhibit potent antinociception with a decrease in the side effects commonly associated with morphine use. In this review we summarize the latest findings regarding the biological and functional characteristics of the opioid receptor heteromers both in vitro and in vivo.
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PMID:

 

24916280

 

[PubMed – as supplied by publisher]