Activation of Na(+)- and Ca(2+)-dependent Mg(2+) extrusion by alpha(1)- and beta-adrenergic agonists in rat liver cells.
The administration of selective alpha(1) (phenylephrine)-, beta (isoproterenol)-, or mixed (epinephrine) adrenergic agonists induces a marked Mg(2+) extrusion from perfused rat livers. In the absence of extracellular Ca(2+), phenylephrine does not induce a detectable Mg(2+) extrusion, isoproterenol-induced Mg(2+) mobilization is unaffected, and epinephrine induces a net Mg(2+) extrusion that is lower than in the presence of extracellular Ca(2+) and quantitatively similar to that elicited by isoproterenol. In the absence of extracellular Na(+), no Mg(2+) 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 extracellular Na(+) or Ca(2+), adrenergic-induced glucose extrusion from the liver is also markedly decreased. Together, these results indicate that liver cells extrude Mg(2+) 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, alternatively, by the changes in cellular Ca(2+) induced by the stimulation of the alpha(1)-adrenoceptor. In addition, the stimulation of the alpha(1)-adrenoceptor appears to activate an auxiliary Ca(2+)-dependent Mg(2+) extrusion pathway. Finally, our data suggest that experimental conditions that affect Mg(2+) mobilization also interfere with glucose extrusion from liver cells.
Fagan
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Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Romani
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000322:Adrenergic Agonists; D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004232:Diuretics; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000584:Amiloride; D005934:Glucagon; D012964:Sodium; C044258:8-chloro-cyclic adenosine monophosphate; D008274:Magnesium; D005947:Glucose; D007545:Isoproterenol; D007099:Imipramine; D010693:Phloretin; D002118:Calcium; D004837:Epinephrine