Opioid efficacy in a C6 glioma cell line stably expressing the delta opioid receptor

Mary J. Clark, Paul J. Emmerson, Alfred Mansour, Huda Akil, James H. Woods, Philip S. Portoghese, Ann E. Remmers, Fedor Medzihradsky

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48 Scopus citations


A C6 glioma cell line stably transfected with the rat delta opioid receptor (C6δ) was used to characterize receptor binding and G protein activation by both peptide and nonpeptide delta opioid ligands. The ligand binding affinities for [3H]naltrindole and [3H]pCl-[D-Pen2,D- Pen5]enkephalin (DPDPE) were similar to those observed in monkey brain membranes. The nonpeptide agonists, BW373U86 and SNC80, as well as peptide agonist [D-Ser2,L-Leu5]enkephalyl-Thr maximally stimulated [35S]GTPγS binding by 640, 654 and 576%, respectively, over basal. The peptide agonists, DPDPE and deltorphin II, both stimulated [35S]GTPγS binding by 375%. Etorphine, diprenorphine, oxymorphindole and 7-spiroindanyloxymorphone were also partial agonists in this assay, although they were less efficacious than deltorphin II. Stimulation of [35S]GTPγS binding by agonists was blocked completely by pertussis toxin pretreatment. Both delta-1 and delta-2 selective antagonists 7-benzylidenenaltrexone and a benzofuran analog of naltrindole displayed high affinity for the cloned receptor (0.04 and 0.08 nM) and antagonized the stimulation of [35S]GTPγS binding by BW373U86 and DPDPE with similar potencies. Other evidence suggesting the lack of receptor subtypes includes the finding that stimulation of [35S]GTPγS binding by receptor subtype selective ligands DPDPE and deltorphin II was not additive. BW373U86, SNC8O and DPDPE maximally inhibited forskolin-stimulated adenylyl cyclase. These cells highly express a homogeneous population of delta opioid receptor that couple to inhibitory G(o)/G(i) proteins. Ligand affinity for the delta opioid receptor correlates with ligand EC50 values for stimulation of [35S]GTPγS binding.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - Nov 1997


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