Low extracellular Mg2+ contraction of arterial muscle: role of protein kinase C and protein tyrosine phosphorylation.

Abstract The effects of extracellular Mg 2+ ion ([Mg 2+ ] 0 ) deficiency on basal tension of isolated rat aortae and rat aortic smooth muscle cell Ca 2+ metabolism were investigated in the present study. The contractions of rat aortae induced by diverse concentrations of low [Mg 2+ ] 0 were potentiated, greatly, by removal of the endothelium or pre-incubation of intact rat aortic rings with l - N G -monomethyl-arginine ( l -NMMA). [Mg 2+ ] 0 deficiency-induced contractions were inhibited, to different degrees, by pre-treatment of the vessels with low concentrations of Go6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein. IC 50 levels found for these three agents were found to be not too different from K i values for these drugs. Pre-treatment of rat aortic smooth muscle cells with Go6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein suppressed, significantly, or almost eliminated both the rapid and stable increments in [Ca 2+ ] i induced by Mg 2+ -free medium. The present findings suggest that both protein kinase C and protein tyrosine phosphorylation appear to play important roles in Mg 2+ deficiency-induced contractions of isolated rat aortic smooth muscle, most likely via phosphorylation of L-type Ca 2+ channels.