The acute administration of a first dose of ethanol (EtOH) to rat liver cells reduces the amount of Mg2+ extruded by a second dose of EtOH or the subsequent addition of adrenergic agonists. In contrast, the Mg2+ extrusion normally elicited by the α1-adrenergic or β-adrenergic agonist does not impair the Mg2+ mobilization induced by the subsequent addition of EtOH. Inhibition of EtOH metabolism by 4-methylpyrazole abolishes almost completely the Mg2+ extrusion induced by the first dose of EtOH, and partially enlarges that elicited by the second dose of alcohol or the subsequent adrenergic stimulation. Ethanol-treated liver cells stimulated by the adrenergic agonist show a reduced level of membrane-bound G αs as well as a reduced cellular cAMP content. Analysis of cellular Mg2+ distribution indicates that EtOH administration decreases the Mg2+ content of the cytoplasm, mitochondria, and endoplasmic reticulum to a comparable extent. These data indicate that acute EtOH administration directly impairs cellular Mg2+ homeostasis and also prevents a further Mg2+ mobilization by additional doses of alcohol or α1-adrenoceptor and β-adrenoceptor agonist by decreasing cytosolic and intraorganelle Mg2+ content and by affecting G-protein membrane distribution/signaling. [ABSTRACT FROM AUTHOR]