Release and inhibition of uptake of 5-hydroxytryptamine in blood platelets in vitro by copper and methyl mercury.

Divalent copper (Cu) and methyl mercury (Met-Hg) are potent inhibitors of the uptake of 5-hydroxytryptamine (5-HT) in rat hypothalamic synaptosomes in vitro. To assess the usefulness of blood platelets as a peripheral model of central serotonergic nerve endings for neurotoxicological studies, for comparison human and rabbit platelets were utilized. Cu inhibited 5-HT uptake into human platelets when platelets were separated from plasma (the IC50 0.7-0.8 microM). Plasma added with platelets abolished the toxic influence of Cu towards platelets. Met-Hg inhibited 5-HT uptake both in washed platelets (the IC50 0.2 microM) and in platelets added in plasma (the IC50s 10-15 microM). The inhibition of uptake by Met-Hg did not depend on buffer Ca and Mg. At low concentrations of Cu, the uptake tended to be more inhibited in the presence of Ca and Mg. Zn and Hg did not affect 5-HT uptake up to 100 microM. Pb inhibited it transiently (28% at 1 microM) in the presence of Ca and Mg. Met-Hg induced the release of endogenous 5-HT from rabbit platelets when they were in a suspension in Ca-free buffer, but Cu did not, even at 100 microM concentration. The results suggest firstly, that blood platelets give results comparable with brain synaptosomes regarding inhibitory effects of metals on 5-HT uptake provided plasma is decanted. Secondly, the inhibition of 5-HT uptake by Cu appears to be purely plasma membrane related but Met-Hg may, in addition, induce release of 5-HT from storage granules.