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.
Kim
D S
DS
Laboratory of Molecular Biology, NIMH, National Institutes of Health, Bethesda, MD 20892, USA.
Chin
H
H
Klee
W A
WA
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