Decrease of the number of opioid receptors and of the responsiveness to morphine during neuronal differentiation induced by 17 beta-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 bindi ng of [H-3]-diprenorphine in human neuroblastoma cells stably transfected w ith the estrogen receptor cDNA (SK-ER3 cell line), A 16-hour exposure of th ese cells with 1 nM 17 beta-estradiol induces a progressive morphological d ifferentiation which appears clearly established 6 days after the suspensio n of the treatment, The binding of [H-3]-diprenorphine was then measured im mediately after the exposure to 17 beta-estradiol (16 h) as well as 6 days later, The results shows that the number of opioid receptors in SK-ER3 cell s is unaffected at 16 h but appears significantly reduced at 6 days, This e ffect is blocked by the estrogen antagonist ICI-182780, and is coincident t o a decrease of the inhibitory effect of morphine on cyclic AMP accumulatio n; Binding experiments performed using selective ligands suggest that the m u subclass of opioid receptors is down-regulated by estradiol in SK-ER3 cel ls.