TY - JOUR
T1 - Interactions between δ opioid receptors and α2A- adrenoceptors
AU - Rios, Carl
AU - Gomes, Ivone
AU - Devi, Lakshmi A.
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Analgesia
KW - Clonidine
KW - Dimerization/oligomerization
KW - G-protein-coupled receptors
KW - Morphine
KW - Opiate
KW - Receptor-receptor interactions
UR - http://www.scopus.com/inward/record.url?scp=9344240868&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1681.2004.04076.x
DO - 10.1111/j.1440-1681.2004.04076.x
M3 - Article
C2 - 15566403
AN - SCOPUS:9344240868
SN - 0305-1870
VL - 31
SP - 833
EP - 836
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 11
ER -