Regulation of mouse delta-opioid receptor gene transcription: involvement of the transcription factors AP-1 and AP-2

J Neurochem. 2000 Apr;74(4):1355-62. doi: 10.1046/j.1471-4159.2000.0741355.x.


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.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Aged
  • Animals
  • Carcinogens / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Genetic Complementation Test
  • Glioma
  • Humans
  • Mice
  • Phosphodiesterase Inhibitors / pharmacology
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / physiology
  • Protein Kinase C / metabolism
  • RNA, Messenger / metabolism
  • Receptor Cross-Talk / physiology
  • Receptors, Opioid, delta / genetics*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factor AP-2
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology*
  • Tumor Cells, Cultured


  • Carcinogens
  • DNA-Binding Proteins
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Receptors, Opioid, delta
  • Transcription Factor AP-1
  • Transcription Factor AP-2
  • Transcription Factors
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • 1-Methyl-3-isobutylxanthine