nalorphine and Neuroblastoma

Exposure of neuronal cells to the chronic presence of opiates leads to a complex series of biochemical events which reflect the changes that result in tolerance and dependence in animals. To achieve a better understanding of the molecular mechanisms underlying these processes, we have examined the effect of agonist efficacy on the regulation of the delta-opioid receptor mRNA in NG108-15 cells. Incubation with various opiates decreased receptor numbers in the order of their efficacy. Northern blot analysis showed that there are 4 size classes of mRNA coding for the delta-opioid receptor in NG108-15 cells even though only one known protein species is found. Moreover, the amount of each transcript is coordinately decreased by long-term etorphine treatment, but not necessarily to the same extent. The etorphine-induced decrease in receptor mRNA was found to be slow in onset, whereas a much more rapid loss of receptor number was observed. This disparity suggests that the down-regulation induced by etorphine can occur both at the levels of receptor protein modification and receptor gene expression, and that the mechanisms of the two processes may be different.

Topics: Animals; Blotting, Northern; Cell Line; Diprenorphine; Down-Regulation; Etorphine; Hybrid Cells; Membrane Proteins; Mice; Morphine; Nalorphine; Narcotic Antagonists; Narcotics; Neuroblastoma; Rats; Receptors, Opioid, delta; RNA, Messenger

Topics: Adenylyl Cyclases; Cell Line; Cyclic AMP; Glioma; Humans; Hybrid Cells; Models, Biological; Morphine; Nalorphine; Neuroblastoma; Neurons; Opium; Protein Conformation; Receptors, Drug; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors