Functional Interactions between μ Opioid and α 2A-Adrenergic Receptors

B. A. Jordan, I. Gomes, C. Rios, J. Filipovska, Lakshmi A. Devi

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

Adrenergic and opioid receptors belong to the rhodopsin family of G-protein coupled receptors, couple to analogous signal transduction pathways, and affect the nociceptive system. Although a number of previous studies have reported functional interactions between these two receptors, the basis for this has not been well explored. We propose that direct receptor-receptor interactions could account, in part, for opioid-adrenergic cross-talk. In this report, we have addressed this using biophysical, biochemical, and pharmacological studies. We show that μ opioid and α2A adrenergic receptors reside in close proximity in live cells using the bioluminescence resonance energy transfer assay. These receptors colocalize to proximal dendrites in primary hippocampal neurons. μ-α2A Receptor complexes can be isolated from heterologous cells or primary neurons coexpressing these receptors. In these cells, the activation of either μ or α2A receptor leads to a significant increase in the level of immunoprecipitable μ-α2A complexes, whereas activation of both receptors leads to a significant decrease. The implications of these effects on signaling were examined using the agonist-mediated increase in G-protein activity and mitogen-activated protein kinase activity. We find that activation of either μ or α2A receptors leads to an increase in the extent of signaling, whereas activation of both receptors leads to a decrease. The increase in signaling by individual ligands and decrease by a combination of ligands is also seen in primary spinal cord neurons endogenously expressing these receptors. Taken together, these results suggest that physical associations between μ and α2A receptors could play a role in the functional interactions between these receptors.

Original languageEnglish (US)
Pages (from-to)1317-1324
Number of pages8
JournalMolecular Pharmacology
Volume64
Issue number6
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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