Effects of chronic exposure of NG108-15 cells to morphine or ethanol on binding of nuclear factors to cAMP-response element.
The gel retardation assay with a single-stranded oligo-DNA of cAMP-response element (CRE) in a somatostatin promoter region was selected to examine the possibility of transcriptional regulation of cAMP-inducible genes by chronic morphine or ethanol treatment of NG108-15 cells. When the nuclear extracts from the cells treated with morphine (50 microM) or ethanol (100 mM) for several days were assayed, the amount of DNA-protein complex was decreased about 30-40% compared to that of the control. The decreased complex was recovered by 1-2 days after withdrawal of the drugs. Treatment of the cells with these drugs for 1 h did not change the amount of the DNA-protein complex. Thus, changes in CRE-binding proteins from the cells treated chronically with morphine or ethanol suggest that these drugs can modulate the expression of cAMP-inducible genes through which tolerance and dependence may develop.
Osugi
T
T
Department of Pharmacology I, Osaka University School of Medicine, Japan.
Taniura
H
H
Ikemoto
M
M
Miki
N
N
D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D004277:DNA, Single-Stranded / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D017362:Cyclic AMP Response Element-Binding Protein; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000431:Ethanol; D009020:Morphine