Effects of manganese on rat brain microsomal Mg 2+Na +K +-ATPase: In Vivo and in vitro studies

Abstract

The effect of manganese on brain microsomal Mg 2+Na +K +-ATPase was examined both in vitro and in vivo. Daily intraperitoneal administration of MnCl 2 · 4H 2O (Mn 2+, 6 mg/kg) to the rats for a period of 90 days produced 10% ( P < 0.05) inhibition in the activity of Mg 2+-ATPase, and 72 and 63% increases in the contents of manganese and copper, respectively, in the microsomal fraction of brain. In in vitro studies, lower concentrations of Mn 2+ activated while higher concentrations inhibited the activity of brain microsomal ATPase. Addition of equal concentrations of Mn 2+ + Cu 2+ (8 m m) in vitro produced 8% inhibition in the activity of Mg 2+-ATPase and 83% inhibition in Na +K +-ATPase. Free Cu 2+ ions were able to antagonize the effect of Mn 2+ on ATPase in vitro and inhibited the activity of Mg 2+Na +K +-ATPase with more pronounced effect of Na +K +-ATPase. The lack of change in the activity of Na +K +-ATPase in the brain microsomes of rats administered manganese, in spite of a significant increase in copper, could not be explained. It is, however, evident that a manganese-induced elevation in brain copper was not responsible for initiating biochemical changes in manganese neurotoxicity.