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.
Young
Andrew
A
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
Berti-Mattera
Liliana
L
Romani
Andrea
A
D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D000077604:Fomepizole; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism; D008274:Magnesium / Q000032:analysis / Q000378:metabolism*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000322:Adrenergic Agonists; D011720:Pyrazoles; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D000077604:Fomepizole; D019204:GTP-Binding Proteins; D008274:Magnesium