INHIBITION OF ATPASE ACTIVITY IN RAT SYNAPTIC PLASMA-MEMBRANES BY SIMULTANEOUS EXPOSURE TO METALS

Inhibition of Na+/K+-ATPase and Mg2+-ATPase activities by in vitro exp osure to Cd2+, Pb2+ and Mn2+ was investigated in rat brain synaptic pl asma membranes (SPMs). Cd2+ and Pb2+ produced a larger maximal inhibit ion of Na+/K+-ATPase than of Mg2+-ATPase activity, Metal concentration s causing 50% inhibition of Na+/K+-ATPase activity (IC50 values) were Cd2+ (0.6 mu M) < Pb2+ (2.1 mu M) < Mn2+ (approximately 3 mM), and the former two metals were substantially more potent in inhibiting SPM ve rsus synaptosomal Na+/K+-ATPase. Dixon plots of SPM data indicated tha t equilibrium binding of metals occurs at sites causing enzyme inhibit ion. In addition, IC50 values for SPM K+-dependent p-nitrophenyl-phosp hatase inhibition followed the same order and were Cd2+ (0.4 mu M) < P b2+ (1.2 mu M) < Mn2+ (300 mu M). Simultaneous exposure to the combina tions Cd2+/Mn2+ or Pb2+/Mn2+ inhibited SPM Na+/K+-ATPase activity syne rgistically (i.e., greater than the sum of the metal-induced inhibitio ns assayed separately), while Cd2+/Pb2+ caused additive inhibition. Si multaneous exposure to Cd2+/Pb2+ antagonistically inhibited Mg2+-ATPas e activity while Cd2+/Mn2+ or Pb2+/Mn2+ additively inhibited Mg2+-ATPa se activity at low Mn2+ concentrations, but inhibited antagonistically at higher concentrations. The similar IC50 values for Cd2+ and Pb2+ v ersus Mn2+ inhibition of Na+/K+-ATPase and the pattern of inhibition/a ctivation upon exposure to two metals simultaneously support similar m odes of interaction of Cd2+ and Pb2+ with this enzyme, in agreement wi th their chemical reactivities.