The stimulation of the α1-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 Ca2+ but in the absence of extracellular Na+. Together, these data suggest that the stimulation of the hepatic α1-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+.
Evidence for the involvement of a small subregion of the endoplasmic reticulum in the inositol trisphosphate receptor-induced activation of Ca2+ inflow in rat hepatocytes