Decrease of the number of opioid receptors and of the responsiveness to morphineduring neuronal differentiation induced by 17beta-estradiol in estrogen receptor-transfected neuroblastoma cells (SK-ER3).
Estrogens modulate the density of opioid receptors in selected brain areas; however, it is not clear whether they exert such an effect directly on the cells which express the opioid receptors. Therefore, we analyzed the binding of [3H]-diprenorphine in human neuroblastoma cells stably transfected with the estrogen receptor cDNA (SK-ER3 cell line). A 16-hour exposure of these cells with 1 nM 17beta-estradiol induces a progressive morphological differentiation which appears clearly established 6 days after the suspension of the treatment. The binding of [3H]-diprenorphine was then measured immediately after the exposure to 17beta-estradiol (16 h) as well as 6 days later. The results shows that the number of opioid receptors in SK-ER3 cells is unaffected at 16 h but appears significantly reduced at 6 days. This effect is blocked by the estrogen antagonist ICI-182780, and is coincident to a decrease of the inhibitory effect of morphine on cyclic AMP accumulation. Binding experiments performed using selective ligands suggest that the micro subclass of opioid receptors is down-regulated by estradiol in SK-ER3 cells.
Maggi
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Department of Endocrinology, Institute of Pharmacological Sciences, University of Milan, Italy. maggir@imiucca.csi.unimi.it
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Pimpinelli
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Maggi
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Martini
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D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004174:Diprenorphine / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014162:Transfection; D014316:Tritium; D014407:Tumor Cells, Cultured
D009292:Narcotic Antagonists; D011960:Receptors, Estrogen; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium; D004174:Diprenorphine; D004958:Estradiol; D009020:Morphine; D000242:Cyclic AMP