Role of nitric oxide in alcohol alteration of beta-endorphin release from hypothalamic cells in primary cultures.
BACKGROUND
Nitric oxide (NO) mediates many pharmacological actions of ethanol. NO's role in regulating ethanol action on hypothalamic beta-endorphin (beta-EP) neurons is not established.


METHODS
In this study, we determined the role of NO in ethanol regulation of beta-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 beta-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 beta-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 NG-nitro-l-arginine-methyl-esther, but not the inactive isomer N-nitro-d-arginine-methyl-esther (d-NAME), inhibited ethanol inhibitory actions on beta-EP release.


CONCLUSIONS
These results suggest that the cyclic guanidine monophosphate/NO pathway is involved in ethanol alteration of hypothalamic beta-EP release.
Boyadjieva
Nadka I
NI
Center for Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick 08901-8525, USA.
Chen
Cui P
CP
Sarkar
Dipak K
DK
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D001615:beta-Endorphin / Q000378:metabolism*
D009569:Nitric Oxide; D000431:Ethanol; D001615:beta-Endorphin