Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells.
Article Details
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Standifer KM, Cheng J, Brooks AI, Honrado CP, Su W, Visconti LM, Biedler JL, Pasternak GW
Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells.
J Pharmacol Exp Ther. 1994 Sep;270(3):1246-55.
- PubMed ID
- 7932177 [ View in PubMed]
- Abstract
Total opioid binding in the human neuroblastoma cell line BE(2)-C has a density similar to that found in brain, with a Bmax value of 383 +/- 60 fmol/mg protein and a KD of 0.4 +/- 0.07 nM for the nonselective opioid antagonist 3H-diprenorphine. Selective assays reveal a binding distribution of mu (38%), delta (16%) and kappa 3 (43%) opioid receptors. There is no observable kappa 1 or kappa 2 binding. The sum of the Bmax values in the selective binding assays (370 +/- 39 fmol/mg protein) approximates closely that observed with 3H-diprenorphine, suggesting that mu, delta and kappa 3 sites account for most of the binding. The binding selectivities of various opiates and opioid peptides in the BE(2)-C cells are similar to those in rat brain. Delta and mu binding are defined easily by traditional selective ligands. The binding profiles also distinguish clearly mu from kappa 3 binding. The selective mu ligand DAMGO competes with mu binding over 35-fold more potently than kappa 3 binding, whereas morphine shows a 10-fold selectivity. Functionally, selective mu, delta and kappa 3 agonists inhibit forskolin-stimulated cAMP accumulation through distinct receptor mechanisms that are pertussis toxin-sensitive. In addition to demonstrating that BE(2)-C cells provide a useful model system for studying mu, kappa 3 and delta receptors, these studies confirm that kappa 3 receptors represent a pharmacologically distinct receptor class in this cell line.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Diprenorphine Delta-type opioid receptor Ki (nM) 0.59 N/A N/A Details Diprenorphine Kappa-type opioid receptor Ki (nM) 0.29 N/A N/A Details Morphine Delta-type opioid receptor Ki (nM) 100 N/A N/A Details Morphine Kappa-type opioid receptor Ki (nM) 11.1 N/A N/A Details Naloxone Delta-type opioid receptor Ki (nM) 1000 N/A N/A Details Naloxone Delta-type opioid receptor Ki (nM) 141.3 N/A N/A Details Naloxone Kappa-type opioid receptor Ki (nM) 1000 N/A N/A Details Naloxone Kappa-type opioid receptor Ki (nM) 13.8 N/A N/A Details