Interference of Methyl Mercury with Monoamine Uptake and Release in Rat Brain Synaptosomes

Abstract

Abstract: Interference of methyl mercury (Met‐Hg), a known neurotoxin, with the high affinity uptake and the release of tritiated dopamine (DA), noradrenaline (NA) and serotonin (5‐HT) was studied in vitro in rat striatal, cortical and hypothalamic synaptosomes respectively. Met‐Hg proved to be a potent inhibitor of uptake; the IC50's were 2.5 μM (DA), 3.2 μM (NA) and 3.4 μM (5‐HT) in 2 min. incubations. The uptake of NA was slightly inhibited already at 0.1–1 μM Met‐Hg whereas DA and 5‐HT were not. The inhibition was rapid, already after 1 min. exposure to 3 μM Met‐Hg the uptake was inhibited totally. The kinetic pattern of the inhibition of DA uptake best agreed with the non‐competitive type. The spontaneous release of monoamines from preloaded synaptosomes was also potently stimulated and was dependent on Met‐Hg concentration. The sensitivity decreased in the order of DA>5‐HT>NA. The apparent inhibition of uptake is probably partly due to the release of the transmitter amine just taken up. Chelation might also contribute to the inhibition of NA and DA uptake. The detailed mechanisms of these phenomena remain to be studied but they may explain some of the direct CNS effects of Met‐Hg.