The basic underlying mechanisms responsible for ethanol intoxication are not well understood. Many studies using intact animals may be confounded by the extreme complexity of the CNS. Studies using homogeneous populations of cells greatly reduce this complexity. We have studied the effects of ethanol using astroglial cells in culture. These studies indicate that ethanol stimulates taurine release in a manner similar to beta-adrenergic agonists, serotonin, and the kappa-opiate, U-50,488. Ethanol-stimulated release is dose-dependent. A concentration of 0.075% ethanol stimulates 50% as much taurine release as a maximally effective concentration of the beta-adrenergic agonist isoproterenol. Thus, concentrations of ethanol associated with intoxication may affect taurine release in the dynamic portion of the dose-response curve where small changes in concentration have large effects on release. Ethanol, like isoproterenol and serotonin, stimulates protein phosphorylation. Phosphorylation of several proteins can be temporally correlated with taurine release. Phosphorylation of these proteins is undetectable before addition of ethanol and is most intense by 3 min, and declines greatly by 30 min. Similarly taurine release is maximal at 3 min and is much reduced after 30 min. Unlike isoproterenol, ethanol does not stimulate increases in intracellular concentrations of adenosine 3',5' monophosphate (cAMP). Thus, ethanol must be affecting protein phosphorylation by a cAMP-independent mechanism. These results demonstrate that ethanol stimulates taurine release at pharmacologically significant doses and indicate that astroglial cells may serve as an excellent model for studying cellular mechanisms underlying acute effects associated with ethanol intoxication.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Unknown (R23)
Project #
5R23AA007155-02
Application #
3445329
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1987-03-01
Project End
1990-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
New York State Department of Health
Department
Type
DUNS #
002436061
City
Menands
State
NY
Country
United States
Zip Code
12204
Madelian, V; Silliman, S; Shain, W (1988) Adenosine stimulates cAMP-mediated taurine release from LRM55 glial cells. J Neurosci Res 20:176-81