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Ligand-Directed Signaling at the Delta Opioid Receptor

Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

Delta opioid receptors (δORs) regulate a number of physiological functions, and agonists for this receptor are being pursued for the treatment of mood disorders, chronic pain, and migraine. A major challenge to the development of these compounds is that, like many G-protein coupled receptors (GPCRs), agonists at the δOR can induce very different signaling and receptor trafficking events. This concept, known as ligand-directed signaling, functional selectivity, or biased agonism, can result in different agonists producing highly distinct behavioral consequences. In this chapter, we highlight the in vitro and in vivo evidence for ligand-directed signaling and trafficking at the δOR. A number of biological implications of agonist-directed signaling at the δOR have been demonstrated. Importantly, ligand-specific effects can impact both acute behavioral effects of delta agonists, as well as the long-term adaptations induced by chronic drug treatment. A better understanding of the specific signaling cascades that regulate these differential behavioral effects would help to guide rational drug design, ultimately resulting in δOR agonists with fewer adverse effects.

Keywords

Pain Receptor trafficking Tolerance 

Notes

Acknowledgements

This work was supported by NIH-NIDA grants DA031243 and DA040688.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of PsychiatryUICChicagoUSA

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