Ligand-directed signaling at the delta opioid receptor

Ana Vicente-Sanchez, Amynah A. Pradhan

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

7 Scopus citations


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.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Number of pages13
StatePublished - 2018

Publication series

NameHandbook of Experimental Pharmacology
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325


  • Pain
  • Receptor trafficking
  • Tolerance


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