Alcohol-induced alterations in phosphoinositide hydrolysis in astrocytes

Cultured astrocytes exposed to ethanol were prelabeled with [3H]inositol and the accumulation of [3H]inositol phosphates was determined following stimulation with norepinephrine (NE). Acute doses of alcohol (25-200 mM) had little effect on phosphoinositide (PI) hydrolysis. However, chronic exposure for 7 days produced significant increases in hydrolysis with ethanol concentrations as low as 50 mM. The onset of alcohol-induced increases occurred within 4 hr of exposure, reaching maximum values by Days 3 to 5. Withdrawal resulted in the return of stimulated PI hydrolysis to pre-alcohol exposure levels after 2 days. The evidence provided suggests that chronic exposure of ethanol alters the alpha-adrenergic receptor characteristics of astrocytes and/or enhances the effector pathway leading to PI hydrolysis at a site distal to the receptor.