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 resul ts in a sizable extrusion of Mg2+ from liver cells. Phenylephrine-induced M g2+ extrusion is almost completely abolished by the removal of extracellula r Ca2+ or in the presence of SKF-96365, an inhibitor of capacitative Ca2+ e ntry. In contrast, Mg2+ extrusion is only partially inhibited by the Ca2+ c hannel blockers verapamil, nifedipine, or (+)BAY-K8644. Furthermore, Mg2+ e xtrusion 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, a nd the coaddition of thapsigargin and phenylephrine does not result in an e nlarged extrusion of Mg2+ from the hepatocytes. Regardless of the agonist u sed, Mg2+ extrusion is inhibited by >90% when hepatocytes are incubated in the presence of physiological Ca2+ 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+ throu gh a Na+-dependent pathway and a Na+-independent pathway, both activated by changes in cellular Ca2+.