Sigma1 binding in a human neuroblastoma cell line |
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Authors: | Jennifer Ryan-Moro Chih-Cheng Chien Kelly M Standifer Gavril W Pasternak |
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Institution: | (1) The Cotzias Laboratory of Neuro-Oncology Memorial Sloan-Kettering Cancer Center and Departments of Neurology & Neuroscience and Pharmacology, Cornell U. Medical College, 10021 New York, NY;(2) Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021 New York, NY |
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Abstract: | Behaviorally, sigma1 agents modulate opioid analgesia. To examine possible mechanisms responsible for these interactions, we have identified a
cell line containing both sigma1 and opioid receptors. 3H](+)-pentazocine binding in BE(2)-C human neuroblastoma cells is high affinity (KD 3.4±0.7 nM) and high density (Bmax 2.98±0.14 pmol/mg protein). Competition studies reveal a selectivity profile similar to that of sigma1 sites in guinea pig brain. (+)-Pentazocine has no effect upon either basal or forskolin-stimulated cyclase in the BE(2)-C
cells, but cAMP accumulation is inhibited by the morphine, DPDPE and naloxone benzoylhydrazone. (+)-Pentazocine at concentrations
as high as 10 μM does not affect this opioid effect, implying that sigma1/opioid interactions are not mediated at the level of the cell. This suggests that their behavioral interactions result from
interacting neural circuits. Although (+)-pentazocine is without effect in the cyclase system, it does block carbachol-stimulated
phosphoinositol turnover (IC50 6.5±1.14 μM). The specificity of the effect is confirmed by the ability of haloperidol (1 μM) to shift the IC50 value of (+)-pentazocine 2-fold to the right.
Special issue dedicated to Dr. Eric J. Simon. |
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Keywords: | Sigma1 binding site human brain opioid receptors BE(2)-C cells |
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