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 Mg(2+) extruded by a second dose of EtOH or the subsequent addition of adrenergic agonists. In contrast, the Mg(2+) extrusion normally elicited by the alpha(1)-adrenergic or beta-adrenergic agonist does not impair the Mg(2+) mobilization induced by the subsequent addition of EtOH. Inhibition of EtOH metabolism by 4-methylpyrazole abolishes almost completely the Mg(2+) 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 Galphas as well as a reduced cellular cAMP content. Analysis of cellular Mg(2+) distribution indicates that EtOH administration decreases the Mg(2+) content of the cytoplasm, mitochondria, and endoplasmic reticulum to a comparable extent. These data indicate that acute EtOH administration directly impairs cellular Mg(2+) homeostasis and also prevents a further Mg(2+) mobilization by additional doses of alcohol or alpha(1)-adrenoceptor and beta-adrenoceptor agonist by decreasing cytosolic and intraorganelle Mg(2+) content and by affecting G-protein membrane distribution/signaling.