Acute effect of EtOH on Mg 2+ homeostasis in liver cells: evidence for the activation of an Na + /Mg 2+ exchanger

American Journal of Physiology-Gastrointestinal and Liver Physi

2005

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α1- and β-Adrenoceptor stimulation elicits Mg2+ extrusion from liver cells in conjunction with hepatic glucose output (T. Fagan and A. Romani. Am J Physiol Gastrointest Liver Physiol 279: G943–G950, 2000.). To characterize the role of intrahepatic glucose on Mg2+ transport, male Sprague-Dawley rats were starved overnight before being anesthetized and used as organ donors. Perfused livers or collagenase-dispersed hepatocytes were stimulated by α1 (phenylephrine)- or β (isoproterenol)-adrenergic agonists. Mg2+ extrusion was assessed by atomic absorbance spectrophotometry. In both experimental models, the administration of pharmacological doses of adrenergic agonists did not elicit Mg2+ extrusion. The determination of cellular Mg2+ indicated an ∼9% decrease in total hepatic Mg2+ content in liver cells after overnight fasting, whereas the ATP level was unchanged. Hepatocytes from starved rats accumulated approximately four times more Mg2+ than liver cells from fed animals. This enlarged Mg2+ accumulation depended in part on extracellular glucose, since it was markedly reduced in the absence of extracellular glucose or in the presence of the glucose transport inhibitor phloretin. The residual Mg2+ accumulation observed in the absence of extracellular glucose was completely abolished by imipramine or removal of extracellular Na+. Taken together, these data indicate 1) that hepatic glucose mobilization is essential for Mg2+ extrusion by adrenergic agonist and 2) that starved hepatocytes accumulate Mg2+ via two distinct pathways, one of which is associated with glucose transport, whereas the second can be tentatively identified as an imipramine-inhibited Na+-dependent pathway.

Section: Chemicalsmentioning

confidence: 99%

“…The lobule portions were weighted, homogenized (20% wt/vol) in the assay medium provided with the RIA kit, boiled for 5 min, and stored at Ϫ20°C until used (42).…”

Section: Chemicalsmentioning

confidence: 99%

Section: Chemicalsmentioning

confidence: 99%

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Role of glucose in modulating Mg²⁺homeostasis in liver cells from starved rats

Torres

Youngner

American Journal of Physiology-Gastrointestinal and Liver Physi

2005

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“…The physiological significance of the unidirectional Na ϩ -dependent Mg 2ϩ efflux from hepatocytes through the apical membrane is equally conjectural and may operate in tandem with the described Na ϩ /bile acid uptake or for direct Mg 2ϩ extrusion (37). It will be interesting to observe whether these transporters are up-regulated in conditions of chronic alcoholism or diabetes when the tissue concentrations of Mg 2ϩ in liver and other tissues dramatically decrease (38,39).…”

Section: Differential Localization and Operation Of Mg 2ϩ Transportersmentioning

confidence: 99%

Differential Localization and Operation of Distinct Mg2+ Transporters in Apical and Basolateral Sides of Rat Liver Plasma Membrane

Cefaratti

Journal of Biological Chemistry

Scarpa³

2000

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Upon activation of specific cell signaling, hepatocytes rapidly accumulate or release an amount of Mg 2؉ equivalent to 10% of their total Mg 2؉ content. Although it is widely accepted that Mg 2؉ efflux is Na ؉ -dependent, little is known about transporter identity and the overall regulation. Even less is known about the mechanism of cellular Mg 2؉ uptake. Using sealed and right-sided rat liver plasma membrane vesicles representing either the basolateral (bLPM) or apical (aLPM) domain, it was possible to dissect three different Mg 2؉ transport mechanisms based upon specific inhibition, localization within the plasma membrane, and directionality. The bLPM possesses only one Mg 2؉ transporter, which is strictly Na ؉ -dependent, bi-directional, and not inhibited by amiloride. The aLPM possesses two separate Mg 2؉ transporters. One, similar to that in the bLPM because it strictly depends on Na ؉ transport, and it can be differentiated from that of the bLPM because it is unidirectional and fully inhibited by amiloride. The second is a novel Ca 2؉ /Mg 2؉ exchanger that is unidirectional and inhibited by amiloride and imipramine. Hence, the bLPM transporter may be responsible for the exchange of Mg 2؉ between hepatocytes and plasma, and vice versa, shown in livers upon specific metabolic stimulation, whereas the aLPM transporters can only extrude Mg 2؉ into the biliary tract. The dissection of these three distinct pathways and, therefore, the opportunity to study each individually will greatly facilitate further characterization of these transporters and a better understanding of Mg 2؉ homeostasis.Magnesium, the second most abundant cation within mammalian cells, is necessary for a variety of metabolic and cellular functions (1-5). Under resting conditions, cellular-free Mg 2ϩ concentration is held at 0.5-0.8 mM, well below its predicted electrochemical equilibrium, and approximately 5 mM Mg 2ϩ is complexed with ATP and other metabolites (1, 5). In several tissues such as heart and liver, specific hormonal or metabolic stimulation causes, within a few minutes, a massive mobilization of cellular Mg 2ϩ (6 -9). Although cytosolic-free Mg 2ϩ undergoes minimal changes, several intracellular signals leading to a cAMP increase induce a loss of 5-10% of total cellular Mg 2ϩ (6 -9). Conversely, signals activating protein kinase C result in an accumulation of Mg 2ϩ and a consequent increase of total cellular Mg 2ϩ by 5-10% (10). These findings underscore the operation of a very powerful Mg 2ϩ transport machinery within the plasma membranes of mammalian cells. Yet, the Mg 2ϩ transporter(s) has not been isolated, and even the basic kinetic properties of Mg 2ϩ cellular transport remain confusing and contradictory. For example, the dependence of Mg 2ϩ release on extracellular Na ϩ has been established in invertebrate and mammalian cells (11-16) but Na ϩ -independent pathways have also been reported (1,8,9,17,18). Equally contradictory are the findings of variable Na ϩ / Mg 2ϩ stoichiometries (1,19), the role of trans-membrane potenti...

“…Net Mg 2ϩ accumulation was estimated as described previously. 21 At the end of the experiment, the heart was homogenized in 10% HNO 3 and extracted overnight. The Mg 2ϩ content in the acid supernatant was measured by atomic absorbance spectrophotometry as described previously.…”

Section: Rat Heart Perfusionmentioning

confidence: 99%

Parallel Stimulation of Glucose and Mg ²⁺ Accumulation by Insulin in Rat Hearts and Cardiac Ventricular Myocytes

Matthews

Scarpa

2000

Circulation Research

Abstract-The stimulation of ␤-adrenoceptors in cardiac cells results in a rapid loss of cellular Mg 2ϩ . Because insulin physiologically counteracts several of the cellular effects mediated by the activation of ␤-adrenoceptors and the elevation of cytosolic cAMP levels, we investigated whether insulin administration could prevent Mg 2ϩ mobilization from rat hearts and ventricular myocytes. Rat hearts were perfused in a retrograde Langendorff system, and the changes in extracellular Mg 2ϩ were measured by atomic absorbance spectrophotometry. Pretreatment of the hearts with 6 nmol/L insulin completely prevented the Mg 2ϩ extrusion induced by the ␤-adrenergic agonist isoproterenol.