Abstract
Background: Nitric oxide (NO) mediates many pharmacological actions of ethanol. NO's role in regulating ethanol action on hypothalamic β-endorphin (β-EP) neurons is not established. Methods: In this study, we determined the role of NO in ethanol regulation of β-EP release from primary cultures of rat fetal mediobasal hypothalamic cells. Real-time polymerase chain reaction was used for messenger RNA (mRNA) detection; radioimmunoassay was used for hormone measurements. Results: Acute ethanol treatment for 3 hr increased the release of β-EP but reduced nitrite levels in the media of hypothalamic cells in primary cultures. In contrast, ethanol exposure for 48 hr reduced the release of β-EP but increased the release of nitrite from these cells. Alcohol treatments altered the expression of neuronal NO synthase mRNA, but not inducible NO synthase mRNA, in a pattern similar to that of nitrite levels. Alcohol treatments blocked sodium nitroprusside-induced increases in the level of cellular cyclic guanidine monophosphate. The nonspecific NO blocker N G-nitro-L-arginine-methyl-esther, but not the inactive isomer N-nitro-D-arginine-methyl-esther (D-NAME), inhibited ethanol inhibitory actions on β-EP release. Conclusions: These results suggest that the cyclic guanidine monophosphate/NO pathway is involved in ethanol alteration of hypothalamic β-EP release.
| Original language | American English |
|---|---|
| Pages (from-to) | 1813-1818 |
| Number of pages | 6 |
| Journal | Alcoholism: Clinical and Experimental Research |
| Volume | 27 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2003 |
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Toxicology
- Psychiatry and Mental health
Keywords
- Ethanol
- Gene Expression
- Inducible Nitric Oxide Synthase (iNOS)
- Neuronal Nitric Oxide Synthase (nNOS)
- β-Endorphin Neurons