Effects of Cd2+, Mn2+, and Al3+ on rat brain synaptosomal uptake of noradrenaline and serotonin.

Cd2+, Mn2+, and Al3+ inhibited synaptosomal amine uptake in a concentration-dependent and time-dependent manner. In the absence of Ca2+, the rank order of inhibition of noradrenaline uptake was: Cd2+ (IC50 = 250 microM) greater than Al3+ (IC50 = 430 microM) greater than Mn2+ (IC50 = 1.50 mM), the IC50 being the concentration of metal ions that gave rise to 50% inhibition of uptake. In the presence of 1 mM Ca2+, the rank order of inhibition of uptake was: Al3+ (IC50 = 330 microM) greater than Cd2+ (IC50 = 540 microM) greater than (IC50 = 1.5 mM). The rank order of inhibition of serotonin uptake without Ca2+ was: Al3+ (IC50 = 370 microM) greater than Cd2+ (IC50 = 610 microM) greater than Mn2+ (IC50 = 3.4 mM) and the rank order in the presence of 1 mM Ca2+ was: Al3+ (IC50 = 290 microM) greater than Cd2+ (IC50 = 1.5 mM) greater than Mn2+ (IC50 = 4.0 mM). Ca2+, at 1 mM, definitely antagonized the inhibitory actions of Cd2+ on noradrenaline and serotonin uptake. Al3+ stimulated noradrenaline uptake at concentrations around 20-250 microM but inhibited this uptake at concentrations exceeding 300 microM in a dose-related fashion. Ca2+, at 1 mM, enhanced both the stimulatory and inhibitory effects of Al3+. Ca2+ also enhanced the inhibitory actions of Al3+ on serotonin uptake. These results, in conjunction with those we have previously published, suggest that Cd2+, Mn2+, and Al3+ exert differential and selective effects on the structure and function of synaptosomal membranes.