alpha(1)-Adrenoceptor-induced Mg2+ extrusion from rat hepatocytes occurs via Na(+)-dependent transport mechanism.
The stimulation of the alpha(1)-adrenergic receptor by phenylephrine results in a sizable extrusion of Mg2+ from liver cells. Phenylephrine-induced Mg2+ extrusion is almost completely abolished by the removal of extracellular Ca2+ or in the presence of SKF-96365, an inhibitor of capacitative Ca2+ entry. In contrast, Mg2+ extrusion is only partially inhibited by the Ca2+-channel blockers verapamil, nifedipine, or (+)BAY-K8644. Furthermore, Mg2+ extrusion is almost completely prevented by TMB-8 (a cell-permeant inhibitor of the inositol trisphosphate receptor), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (an intracellular Ca2+-chelating agent), or W-7 (a calmodulin inhibitor) Thapsigargin can mimic the effect of phenylephrine, and the coaddition of thapsigargin and phenylephrine does not result in an enlarged extrusion of Mg2+ from the hepatocytes. Regardless of the agonist used, Mg2+ extrusion is inhibited by >90% when hepatocytes are incubated in the presence of physiological Ca(2+) but in the absence of extracellular Na(+). Together, these data suggest that the stimulation of the hepatic alpha(1)-adrenergic receptor by phenylephrine results in an extrusion of Mg2+ through a Na(+)-dependent pathway and a Na(+)-independent pathway, both activated by changes in cellular Ca2+.
Fagan
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Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, Ohio 44106-4970, USA.
Romani
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A
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012964:Sodium / Q000502:physiology*
D002147:Calmodulin; D011942:Receptors, Adrenergic, alpha; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D008274:Magnesium; D002118:Calcium