Metal inhibition of calmodulin activity in monkey brain

Studies were conducted to investigate the effect of vanadium (V5+), cadmium (Cd2+), mercury (Hg2+), aluminium (Al3+), lead (Pb2+) and manganese (Mn2+) ions on calmodulin (CaM)-related Ca2+-ATPase activity in rhesus monkey (Macaca mulatta) brain (RMB). The cerebral cortex of RMB was dissected and homogenized in 10% sucrose buffer, and synaptic plasma membranes (SPM) were prepared. Ca2+-ATPase activity was determined by the inorganic phosphate method. Different concentrations of metal ions were incubated with RMB fractions containing endogenous CaM and RMB fractions without CaM. The results show that no metal ion inhibited the basal enzyme but that they showed a profound inhibition of total Ca2+-ATPase containing CaM. The order of potency of metals was Hg greater than Cd greater than Pb greater than Mn greater than Al greater than V. Exogenous addition of CaM restored the metal-inhibited enzyme activity to near the normal level. The basal enzyme, when reconstituted with CaM, showed sensitivity to metal ions. These data, presented for the first time in non-human primate brain, indicate that the metal ions inhibit CaM activity in RMB.