Activation of Na+- and Ca2+-dependent Mg2+ extrusion by alpha(1)- and beta-adrenergic agonists in rat liver cells

The administration of selective a 1 (phenylephrine)-, beta (isoproterenol)- , or mixed (epinephrine) adrenergic agonists induces a marked Mg2+ extrusio n from perfused rat livers. In the absence of extracellular Ca2+, phenyleph rine does not induce a detectable Mg2+ extrusion, isoproterenol-induced Mg2 + mobilization is unaffected, and epinephrine induces a net Mg2+ extrusion that is lower than in the presence of extracellular Ca2+ and quantitatively similar to that elicited by isoproterenol. In the absence of extracellular Na+, no Mg2+ is extruded from the liver irrespective of the agonist used. Similar results are observed in perfused livers stimulated by glucagon or 8 -chloroadenosine 3',5'-cyclic monophosphate. In the absence of extracellula r Na+ or Ca2+, adrenergic-induced glucose extrusion from the liver is also markedly decreased. Together, these results indicate that liver cells extru de Mg2+ primarily via a Na+-dependent mechanism. This extrusion pathway can be activated by the increase in cellular cAMP that follows the stimulation by glucagon or a specific beta -adrenergic receptor agonist or, alternativ ely, by the changes in cellular Ca2+ induced by the stimulation of the alph a (1)-adrenoceptor. In addition, the stimulation of the alpha (1)-adrenocep tor appears to activate an auxiliary Ca2+-dependent Mg2+ extrusion pathway. Finally, our data suggest that experimental conditions that affect Mg2+ mo bilization also interfere with glucose extrusion from liver cells.