Agonist-induced state of the delta-opioid receptor that discriminates between opioid peptides and opiate alkaloids

Author(s): Zastrow von M, Keith DE, Evans CJ


We report a novel agonist-induced change in delta-opioid receptor binding properties in NG108-15 cells. Pretreatment of these cells with opioid agonists substantially diminishes the binding of peptide agonists and a peptide antagonist to opioid receptors in intact cells or membrane preparations. However, similar agonist-induced changes in the binding of opiate alkaloid agonists and antagonists were not detected. The change in opioid peptide binding occurs rapidly at 37 degrees (t1/2 approximately 10 min) but is not induced by agonist treatment at 4 degrees. Because of its lability at 37 degrees, the binding change is only detected when equilibrium binding assays are performed at 4 degrees. Both alkaloid and peptide agonists induce the binding change in a dose-dependent manner, with an ED50 for etorphine of approximately 10 nM. The induction of the binding change is completely blocked by the opiate antagonist naloxone. Stimulation of muscarinic receptors (which, like opioid receptors, inhibit adenylate cyclase in these cells) does not induce or block the binding change. These data reveal the operation of a homologous regulation mechanism that rapidly diminishes the interaction of delta-subtype opioid receptors with peptide ligands but does not detectably change the interaction of receptors with alkaloid ligands.

Similar Articles

Enhanced morphine analgesia in mice lacking beta-arrestin 2

Author(s): Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, et al.

Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence

Author(s): Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG, et al.

Ligand-directed signalling within the opioid receptor family

Author(s): Pradhan AA, Smith ML, Kieffer BL, Evans CJ

μ-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization

Author(s): McPherson J, Rivero G, Baptist M, Llorente J, Al-Sabah S, et al.

Morphine-like opiates selectively antagonize receptor-arrestin interactions

Author(s): Molinari P, Vezzi V, Sbraccia M, Grò C, Riitano D, et al.

Pharmacological characterization of AR-M1000390 at human delta opioid receptors

Author(s): Marie N, Landemore G, Debout C, Jauzac P, Allouche S

SK-N-BE: a human neuroblastoma cell line containing two subtypes of delta-opioid receptors

Author(s): Polastron J, Mur M, Mazarguil H, Puget A, Meunier JC, et al.

ßarrestin1-biased agonism at human δ-opioid receptor by peptidic and alkaloid ligands

Author(s): Aguila B, Coulbault L, Davis A, Marie N, Hasbi A, et al.

Molecular control of δ-opioid receptor signalling

Author(s): Fenalti G, Giguere PM, Katritch V, Huang XP, Thompson AA, et al.

Development and validation of a genetic algorithm for flexible docking

Author(s): Jones G, Willett P, Glen RC, Leach AR, Taylor R, et al.

Agonist-selective mechanisms of GPCR desensitization

Author(s): Kelly E, Bailey CP, Henderson G

Recovery from mu-opioid receptor desensitization after chronic treatment with morphine and methadone

Author(s): Quillinan N, Lau EK, Virk M, von Zastrow M, Williams JT

Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes

Author(s): Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, et al.