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

The effects of some heavy metals on the initial high affinity uptake and spontaneous release of tritiated dopamine ( 3 H‐DA), noradrenaline ( 3 H‐NA) and 5‐hydroxytryptamine ( 3 H‐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 Cu 2+ was most potent, inhibiting 3 H‐DA and 3 H‐5‐HT uptake nearly completely while inhibition of 3 H‐NA uptake varied. 3 H‐DA uptake was in addition inhibited slightly by Zn 2+ , sometimes by Sn 2+ but never by Co 2+ , Hg 2+ or Mn 2+ . Unexpectedly Pb 2+ and Cd 2+ tended to increase the synaptosomal 3 H‐DA uptake. 3 H‐5‐HT uptake was affected least while that of 3 H‐NA showed some diversity. Zn 2+ , Pb 2+ and Sn 2+ induced inhibition of 3 H‐NA uptake possibly by direct interference with 3 H‐NA. As to the spontaneous release of tritiated amines during short incubation from preloaded synaptosomes, Cd 2+ decreased that of 3 H‐DA at high concentrations but Hg 2+ , Pb 2+ , Sn 2+ and Zn 2+ were ineffective. The results suggest that in vitro the uptake and the release of 3 H‐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.