Effect of Heavy Metals on Dopamine, Noradrenaline and Serotonin Uptake and Release in Rat Brain Synaptosomes

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Abstract
The effects of some heavy metals on the initial high affinity uptake and spontaneous release of tritiated dopamine (3H‐DA), noradrenaline (3H‐NA) and 5‐hydroxytryptamine (3H‐5‐HT) were studied in vitro in rat striatal, cortical and hypothalamic synaptosomes, respectively. As uptake inhibitors, metals were quite inactive in these conditions. At 10 μM Cu2+ was most potent, inhibiting 3H‐DA and 3H‐5‐HT uptake nearly completely while inhibition of 3H‐NA uptake varied. 3H‐DA uptake was in addition inhibited slightly by Zn2+, sometimes by Sn2+ but never by Co2+, Hg2+ or Mn2+. Unexpectedly Pb2+ and Cd2+ tended to increase the synaptosomal 3H‐DA uptake. 3H‐5‐HT uptake was affected least while that of 3H‐NA showed some diversity. Zn2+, Pb2+ and Sn2+ induced inhibition of 3H‐NA uptake possibly by direct interference with 3H‐NA. As to the spontaneous release of tritiated amines during short incubation from preloaded synaptosomes, Cd2+ decreased that of 3H‐DA at high concentrations but Hg2+, Pb2+, Sn2+ and Zn2+ were ineffective. The results suggest that in vitro the uptake and the release of 3H‐DA are more affected than those of other amines. The inhibitory mechanisms of monoamine uptake may include both direct effects on synaptosomes and indirect ones by interference with the amines themselves.