Effect of Repeated Doses of Ethanol on Hepatic Mg²⁺ Homeostasis and Mobilization

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 Gαs 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.