The δ opioid receptor agonist SNC80 selectively activates heteromeric μ-δ Opioid receptors

Matthew D. Metcalf, Ajay S. Yekkirala, Michael D. Powers, Kelley F. Kitto, Carolyn A. Fairbanks, George L. Wilcox, Philip S. Portoghese

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Coexpressed and colocalized μ- and δ-opioid receptors have been established to exist as heteromers in cultured cells and in vivo. However the biological significance of opioid receptor heteromer activation is less clear. To explore this significance, the efficacy of selective activation of opioid receptors by SNC80 was assessed in vitro in cells singly and coexpressing opioid receptors using a chimeric G-protein-mediated calcium fluorescence assay, SNC80 produced a substantially more robust response in cells expressing μ-δ heteromers than in all other cell lines. Intrathecal SNC80 administration in μ- and δ-opioid receptor knockout mice produced diminished antinociceptive activity compared with wild type. The combined in vivo and in vitro results suggest that SNC80 selectively activates μ-δ heteromers to produce maximal antinociception. These data contrast with the current view that SNC80 selectively activates δ-opioid receptor homomers to produce antinociception. Thus, the data suggest that heteromeric μ-δ receptors should be considered as a target when SNC80 is employed as a pharmacological tool in vivo.

Original languageEnglish (US)
Pages (from-to)505-509
Number of pages5
JournalACS Chemical Neuroscience
Issue number7
StatePublished - Jul 18 2012


  • SNC80
  • antinociception
  • knockout
  • δ opioid receptor
  • μ opioid receptor
  • μ-δheteromer


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