32 Scopus citations

Abstract

1. Several studies have reported functional interactions between different subtypes of opioid and α2A-adrenoceptors in the induction of spinal cord analgesia. The mechanisms underlying this phenomenon are not well characterized. We propose that direct receptor-receptor associations could account for some of the observed functional interactions. In the present study, we examined the presence of δ opioid receptors and α2A- adrenoceptors in interacting complexes and the functional implications of such interactions on receptor activity. 2. Using the proximity based bioluminescence resonance energy transfer (BRET) assay, we found that the δ opioid receptors and α2A-adrenoceptors are in close enough proximity (< 100 Å) in live cells that can foster physical interactions. 3. Using coimmunoprecipitation of differentially epitope-tagged receptors, we found that δ opiate receptors exist in interacting complexes with α2A-adrenoceptors in heterologous cells. 4. Finally, using receptor activity mediated neurite outgrowth in Neuro 2A cells as a physiological readout, we found that interactions between δ opiate receptors and α2A-adrenoceptors have functional consequences. The expression of α2A-adrenoceptors is sufficient to promote δ opiate receptor-mediated neurite outgrowth, suggesting that the presence of inactive α2A-adrenoceptors can enhance δ opiate receptor-mediated signalling. 5. Taken together, these findings suggest that modulation of receptor function as a result of physical associations between δ opiate receptors and α2A-adrenoceptors may account for the observed synergy between opiate and adrenergic agonists in spinal analgesia.

Original languageEnglish
Pages (from-to)833-836
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume31
Issue number11
DOIs
StatePublished - Nov 2004

Keywords

  • Analgesia
  • Clonidine
  • Dimerization/oligomerization
  • G-protein-coupled receptors
  • Morphine
  • Opiate
  • Receptor-receptor interactions

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