Regulation of mouse delta-opioid receptor gene transcription: involvement of the transcription factors AP-1 and AP-2.
The aim of this study was to examine the effects of the phorbol ester O-tetradecanoylphorbol 13-acetate (TPA) and forskolin on delta-opioid receptor gene transcription. Treatment of NG108-15 cells with TPA (100 nM) for 48 h increased delta-opioid receptor mRNA levels, whereas different concentrations of forskolin induced a transient down-regulation of mRNA 5 h after treatment, followed by increased mRNA levels after 48 h. Reporter gene assays in transiently transfected NG108-15 cells in combination with electrophoretic mobility shift assays indicate that the increase of delta-opioid receptor mRNA after stimulation with TPA is mediated by transcription factor AP-1, which binds 355 bp upstream of the start codon within the gene promoter. The forskolin-induced mRNA increase is mediated neither by a cyclic AMP-response element nor indirectly by AP-1 up-regulation. Reporter gene assays, mutational analysis, and electrophoretic mobility shift assays revealed that delta-opioid receptor gene regulation by forskolin is mediated by transcription factor AP-2, which binds to an element 157 bp upstream of the start codon.
Wöltje
M
M
Institute of Pharmacology and Toxicology, University of Magdeburg, Germany.
Kraus
J
J
Höllt
V
V
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000368:Aged; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005816:Genetic Complementation Test; D005910:Glioma; D006801:Humans; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004268:DNA-Binding Proteins; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine