Agonist regulation of the expression of the delta opioid receptor in NG108-15 cells.
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.
Laboratory of Molecular Biology, NIMH, National Institutes of Health, Bethesda, MD 20892, USA.
D S
DS
Kim
H
H
Chin
W A
WA
Klee
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D004174:Diprenorphine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005048:Etorphine / Q000494:pharmacology; D006822:Hybrid Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology; D009269:Nalorphine / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009294:Narcotics / Q000819:agonists* / Q000378:metabolism / Q000494:pharmacology; D009447:Neuroblastoma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000378:metabolism
D008565:Membrane Proteins; D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D004174:Diprenorphine; D005048:Etorphine; D009020:Morphine; D009269:Nalorphine