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Research ArticleArticle

Opioid Receptor Homo- and Heterodimerization in Living Cells by Quantitative Bioluminescence Resonance Energy Transfer

Danxin Wang, Xiaochun Sun, Laura M. Bohn and Wolfgang Sadée
Molecular Pharmacology June 2005, 67 (6) 2173-2184; DOI: https://doi.org/10.1124/mol.104.010272
Danxin Wang
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Xiaochun Sun
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Laura M. Bohn
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Wolfgang Sadée
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Abstract

Opioid receptors have been shown to dimerize or oligomerize among themselves and each other, affecting their functional properties. This study used bioluminescence resonance energy transfer (BRET) between the μ, δ, and κ opioid receptors to study opioid receptor aggregation in transfected human embryonic kidney 293 cells. Titration of receptor levels indicated that all three opioid receptors have a similar affinity to form homo- or hetero-oligomers in combination with any other opioid receptor type. In contrast, none of the opioid receptors formed detectable oligomers with the muscarinic M2 receptor, indicating that interactions among opioid receptors are selective. The formation of opioid receptor dimers, rather than higher order oligomers, is supported by binding kinetics in competition experiments between labeled and unlabeled receptors. Opioid receptor dimerization occurred at physiological temperatures upon receptor biosynthesis, before trafficking to the plasma membrane. Moreover, using BRET, coimmunoprecipitation, receptor binding, and G protein coupling, we demonstrate for the first time functional μ opioid receptor-κ opioid receptor heterodimerization. These combined results demonstrate that opioid receptors can undergo homo- and heterodimerization, a process with potential implications for opioid physiology and pharmacology.

  • Received December 13, 2004.
  • Accepted March 11, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (6)
Molecular Pharmacology
Vol. 67, Issue 6
1 Jun 2005
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Research ArticleArticle

Opioid Receptor Homo- and Heterodimerization in Living Cells by Quantitative Bioluminescence Resonance Energy Transfer

Danxin Wang, Xiaochun Sun, Laura M. Bohn and Wolfgang Sadée
Molecular Pharmacology June 1, 2005, 67 (6) 2173-2184; DOI: https://doi.org/10.1124/mol.104.010272

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Research ArticleArticle

Opioid Receptor Homo- and Heterodimerization in Living Cells by Quantitative Bioluminescence Resonance Energy Transfer

Danxin Wang, Xiaochun Sun, Laura M. Bohn and Wolfgang Sadée
Molecular Pharmacology June 1, 2005, 67 (6) 2173-2184; DOI: https://doi.org/10.1124/mol.104.010272
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