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Chronic ethanol increases N-methyl-D-aspartate-stimulated nitric oxide formation but not receptor density in cultured cortical neurons.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chandler, L. Judson Sutton, Granger Norwood, Daphne Sumners, Colin Crews, Fulton T. |
| Copyright Year | 1997 |
| Abstract | The effects of prolonged ethanol exposure on excitatory amino acid receptor stimulated nitric oxide (NO) formation were examined in primary rat cortical neuronal cultures. Chronic ethanol (4 days, 100 mM) potentiated N-methyl-D-aspartate (NMDA)-stimulated NO formation as determined by measuring the conversion of [3H]arginine to [3H]citrulline. In contrast, chronic ethanol had no effect on NO formation stimulated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxalonepropionic acid, or the calcium ionophore ionomycin. Potassium chloride-stimulated NO formation was also enhanced by chronic ethanol treatment, but this effect was not seen in the presence of the ionotropic glutamate receptor antagonists MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione. Immunoblot analysis of expression of NR1, NR2A, and NR2B receptor subunits showed no difference between control and chronic ethanol-treated cultures. In support of this apparent lack of change in receptor density, there was no difference in the specific binding of 125I-MK-801 between control and chronic ethanol-treated groups. These results demonstrate that prolonged ethanol exposure selectively enhanced NMDA receptor-stimulated NO formation, which may play an important role in alcohol dependence, withdrawal, and alcohol-associated brain damage. These results also suggest that chronic ethanol-induced increases in NMDA receptor function may not be due to a simple increase in the number of NMDA receptors or change in NMDA receptor subunit composition but may instead reflect more complicated and subtle changes. |
| Starting Page | 769 |
| Ending Page | 774 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/51/5/733.full.pdf |
| PubMed reference number | 9145911v1 |
| Volume Number | 51 |
| Issue Number | 5 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alcoholic Intoxication, Chronic Aspartic Acid Brain Injuries Calcium Dizocilpine Maleate Ethanol Excitatory Amino Acid Antagonists Excitatory Amino Acids GRIN2A wt Allele Glutamate Receptor Glutamic Acid Ionomycin Ionophores Kainate N-Methyl-D-Aspartate Receptors N-Methylaspartate Potassium Chloride Receptors, Amino Acid Thioctic Acid nitric oxide biosynthetic process |
| Content Type | Text |
| Resource Type | Article |
