Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells.

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
DiprenorphineDelta-type opioid receptorKi (nM)0.59N/AN/ADetails
DiprenorphineKappa-type opioid receptorKi (nM)0.29N/AN/ADetails
MorphineDelta-type opioid receptorKi (nM)100N/AN/ADetails
MorphineKappa-type opioid receptorKi (nM)11.1N/AN/ADetails
NaloxoneDelta-type opioid receptorKi (nM)1000N/AN/ADetails
NaloxoneDelta-type opioid receptorKi (nM)141.3N/AN/ADetails
NaloxoneKappa-type opioid receptorKi (nM)1000N/AN/ADetails
NaloxoneKappa-type opioid receptorKi (nM)13.8N/AN/ADetails