Effects of Heavy Metals in Transport of GABA in Cat Brain Synaptosome

Lee, Young Woo

Abstract

The administration of Aluminium had shown the result of neurofibrillary degeneration in encephalopathy of Alzhheimer's desease and cadmium chloride caused the damage of cells of the cerebral cortex. The neurological signs of chronic manganese intoxication were related to Wilson's disease and Parkinsonism. Subsequently the heavy metals were found to be a neurotoxic agent. The author had studied the effect of Al3+, Cd2+ and Mn2+ on transport of synaptosomal GABA and on synaprosomal Na-K-ATPase activity in cat brain. The results were as follows : 1) Synaptosomal GABA uptake was increased within 10 minutes of the incubation and after that time the uptake was not increased and the increase was entirely inhibited by adding cold 5 mM GABA. 2) Al3+, Cd2+ and Mn2+ inhibited the rates of uptake of synaptosomal GABA in a dose-dependent fashion, particularly in Al3+. It was found that the uptake was not made by irreversible damage of synaptosomal uptake. 3) The effect of Al3+ on synaptosomal GABA uptake had shown the inhibition by mixed type fashion of kinetic analysis. 4) Al3+, Cd2+ and Mn2+ inhibited the rates of uptake of synaptosomal Na-K-ATPase activity in a dose-dependent fashion. The concentrations Al3+, Cd2+ and Mn2+ that would give 50% inhibition(IC50) of synaptosomal Na-K-ATPase activity were 1.1x10(-4), 5.6x10(-3) and 6.3x10(-3) M, respectively. 5) Al3+ had shown the inhibition of synaptosomal GABA uptake and Na-K-ATPase activity. In contrast the rate of 88% inhibition of Na-K-ATPase activity had got the rate of 5% inhibition of GABA uptake. The results suggest that the transport(uptake) os synaptosomal GABA is occured by Na+ and also the heavy metal may inhibit the uptake with another mechanism. And then the heavy metal might have the toxic effect of the inhibition of neurotransmitter transport in nerve cells.