dihydromorphine and Neuroblastoma

The present study showed that the glucocorticoid/progesterone antagonists, 17 beta-hydroxy-1 1 beta-(4-dimethylamino-phenyl-1)-17-(prop-1-ynyl)estra-4,9-dien+ ++-3-one (RU486) and 17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl-1)-17-(propan-3-ol)estra-4,9-dien-3-o ne (ZK 98299), inhibit the binding of labeled dihydromorphine to mu-opioid receptors present on membrane preparations derived from rat and mouse brain, as well as from human neuroblastoma cells. The inhibitory effect of RU486 was dose-dependent and linked to a decrease of the affinity of labeled dihydromorphine to the mu-opioid receptors. Kinetic experiments have shown that RU486 induces a decrease of the association rate constant (k + 1) of dihydromorphine. RU486 also proved able to dissociate the dihydromorphine-mu-opioid receptor complex, although at a rate slower than that exhibited by unlabeled dihydromorphine. Finally, the addition of NaCl (100 mM) to the incubation buffer induced a 50% decrease of the inhibitory effect of RU486. A 6-day treatment of neuroblastoma cells with RU486 eliminated the inhibitory effect morphine exerts on the intracellular accumulation of cyclic AMP induced by prostaglandin E1. These results indicate that RU-486 may interact with brain mu-opioid receptors in vitro, by decreasing the affinity of opioid ligands.

Topics: Analgesics; Animals; Dihydromorphine; Diprenorphine; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Female; Gonanes; Hormone Antagonists; Humans; In Vitro Techniques; Male; Membranes; Mice; Mifepristone; Narcotic Antagonists; Narcotics; Nerve Tissue; Nervous System Neoplasms; Neuroblastoma; Progestins; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Sodium; Tumor Cells, Cultured

Incubation for 48 hours of C6 glioma cell cultures with 10(-4)M tricyclic antidepressant desipramine gave rise to a quantitative increase of total lipids and to qualitative modifications of glycosphinegolipids involving detection by thin-layer chromatography of spots migrating according to cerebroside and sulfatide and presence of an abnormal ganglioside pattern. These lipid modifications were associated with the appearance of stereospecific binding of opiates (dihydromorphine) with a dissociation constant of 30-60 nM. These results favor an important role of lipids in opioid receptor function.

Topics: Animals; Cell Transformation, Neoplastic; Desipramine; Dihydromorphine; Glioma; Lipid Metabolism; Neuroblastoma; Rats; Receptors, Opioid; Stereoisomerism

Topics: Adenylyl Cyclases; Animals; Cations, Divalent; Cations, Monovalent; Cell Line; Cyclic AMP; Dihydromorphine; Enzyme Activation; Kinetics; Mice; Naloxone; Neoplasms, Experimental; Neuroblastoma; Phospholipases; Prostaglandins E; Receptors, Opioid