Retinoic acid-induced increase in delta-opioid receptor and N-methyl-D-aspartate receptor mRNA levels in neuroblastoma x glioma (NG108-15) cells.

We determined the effects of all-trans retinoic acid (RA) on the levels of delta opioid receptor (DOR) mRNA and N-Methyl-D-Aspartate receptor (NMDAR1) mRNA in neuroblastoma x glioma hybrid cells (NG108-15) by use of quantitative solution hybridization assays. The assays utilized riboprobes complementary to major portions of the coding region of the DOR and NMDAR1 cDNAs. At 10 microM RA a 3-fold increase in DOR mRNA at 48 h, and later (144 h) alterations were observed in NMDAR1 mRNA levels. Northern blot analysis revealed six transcripts for DOR mRNA ranging in size from 8.7 to 2.0 Kb, and three transcripts for NMDAR1 mRNA ranging in size from 4.1 to 3.5 Kb. Neither the size nor the fractional band intensity was affected by RA treatment. The delayed induction of DOR mRNA suggests an indirect mechanism by which RA acts on transcription of this gene. A surprising induction of DOR mRNA by the protein synthesis inhibitor cycloheximide (CHX) suggests that either a repressor molecule or degrading enzymes/proteases may regulate basal levels of this mRNA. Treatment with RA resulted in a concentration- and time-dependent morphological differentiation characterized by increased size of the cell body and the appearance of numerous short and long processes.