Delayed restoration of Mg2+ content and transport in liver cells following ethanol withdrawal.
Liver cells from rats chronically fed a Lieber-De Carli diet for 3 wk presented a marked decreased in tissue Mg(2+) content and an inability to extrude Mg(2+) into the extracellular compartment upon stimulation with catecholamine, isoproterenol, or cell-permeant cAMP analogs. This defect in Mg(2+) extrusion was observed in both intact cells and purified liver plasma membrane vesicles. Inhibition of adrenergic or cAMP-mediated Mg(2+) extrusion was also observed in freshly isolated hepatocytes from control rats incubated acutely in vitro with varying doses of ethanol (EtOH) for 8 min. In this model, however, the defect in Mg(2+) extrusion was observed in intact cells but not in plasma membrane vesicles. In the chronic model, upon removal of EtOH from the diet hepatic Mg(2+) content and extrusion required approximately 10 days to return to normal level both in isolated cells and plasma membrane vesicles. In hepatocytes acutely treated with EtOH for 8 min, more than 60 min were necessary for Mg(2+) content and extrusion to recover and return to the level observed in EtOH-untreated cells. Taken together, these data suggest that in the acute model the defect in Mg(2+) extrusion is the result of a limited refilling of the cellular compartment(s) from which Mg(2+) is mobilized upon adrenergic stimulation rather than a mere defect in adrenergic cellular signaling. The chronic EtOH model, instead, presents a transient but selective defect of the Mg(2+) extrusion mechanisms in addition to the limited refilling of the cellular compartments.
Torres
Lisa M
LM
Dept. of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Cefaratti
Christie
C
Berti-Mattera
Liliana
L
Romani
Andrea
A
D000322:Adrenergic Agonists / Q000494:pharmacology; D000428:Alcohol Drinking / Q000009:adverse effects*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors
D000322:Adrenergic Agonists; D010656:Phenylephrine; D000431:Ethanol; D003994:Bucladesine; D008274:Magnesium; D007545:Isoproterenol