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Ethanol increases delta-opioid receptor gene expression in neuronal cell lines
M E Charness1, G Hu, R H Edwards
1Department of Neurology, Harvard Medical School, West Roxbury Veterans Affairs Medical Center, MA 02132.
Molecular Pharmacology
|December 1, 1993
Summary
Long-term ethanol exposure increases delta-opioid receptor (DOR) expression in neural cells by boosting DOR messenger RNA (mRNA) levels. This suggests ethanol influences receptor regulation at the gene expression level.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Ethanol (alcohol) is known to affect the central nervous system.
- Delta-opioid receptors (DOR) are important targets for opioid drugs and endogenous peptides.
- Understanding how ethanol interacts with opioid receptors is crucial for comprehending alcohol's neurobiological effects.
Purpose of the Study:
- To investigate the mechanism by which long-term ethanol treatment alters delta-opioid receptor (DOR) expression in neural cell lines.
- To determine if ethanol affects DOR gene expression and ligand binding.
- To explore the relationship between DOR expression, cAMP levels, and ethanol concentration.
Main Methods:
- Utilized four related clonal neural cell lines (NG108-15, N18TG2, N4TG1, N1E-115).
- Assessed [3H]diprenorphine binding to intact cells after ethanol incubation.
- Measured DOR gene expression using Northern blot analysis to quantify DOR mRNA abundance.
- Evaluated the functional consequences on cAMP signaling pathways.
Main Results:
- Long-term ethanol treatment significantly increased [3H]diprenorphine binding, indicating higher DOR expression.
- Ethanol exposure led to a dose-dependent increase in DOR expression.
- Northern blot analysis revealed a substantial increase in DOR mRNA levels following ethanol treatment.
- Ethanol also increased basal cAMP levels in most cell lines studied.
Conclusions:
- Clinically relevant ethanol concentrations up-regulate delta-opioid receptor (DOR) expression.
- The primary mechanism involves an increase in the abundance of DOR mRNA.
- Discrepancies between mRNA and binding levels suggest potential post-transcriptional regulation by ethanol, possibly affecting translation or receptor processing.