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INTERACTIONS BETWEEN δ OPIOID RECEPTORS AND α 2A ‐ADRENOCEPTORS
Author(s) -
Rios Carl,
Gomes Ivone,
Devi Lakshmi A
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.04076.x
Subject(s) - receptor , δ opioid receptor , adrenergic receptor , opioid , μ opioid receptor , neuroscience , opiate , microbiology and biotechnology , chemistry , biology , biophysics , medicine
SUMMARY 1. Several studies have reported functional interactions between different subtypes of opioid and α 2A ‐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 α 2A ‐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 α 2A ‐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 α 2A ‐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 α 2A ‐adrenoceptors have functional consequences. The expression of α 2A ‐adrenoceptors is sufficient to promote δ opiate receptor‐mediated neurite outgrowth, suggesting that the presence of inactive α 2A ‐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 α 2A ‐adrenoceptors may account for the observed synergy between opiate and adrenergic agonists in spinal analgesia.