The stimulation of the alpha(1)-adrenergic receptor with phenylephrine results in the significant extrusion of Mg(2+) from the rat heart and cardiomyocytes. Phenylephrine-induced Mg(2+) extrusion is prevented by the removal of extracellular Ca(2+) or by the presence of Ca(2+)-channel blockers such as verapamil, nifedipine, or (+)BAY-K8644. Mg(2+) extrusion is almost completely inhibited by PD98059 (a MAP kinase inhibitor). The simultaneous addition of 5mM Ca(2+) and phenylephrine increases the extrusion of Mg(2+) from perfused hearts and cardiomyocytes. This Mg(2+) extrusion is inhibited by more than 90% when the hearts are preincubated with PD98059. ERKs are activated by perfusion with either phenylephrine or 5mM Ca(2+). This ERK activation is inhibited by PD98059. Overall, these results suggest that stimulating the cardiac alpha(1)-adrenergic receptor by phenylephrine causes the extrusion of Mg(2+) via the Ca(2+)-activated, Na(+)-dependent transport pathway, and the ERKs assists in Mg(2+) transport in the heart.