Trimethyltin inhibits uptake of neurotransmitters into mouse forebrain synaptosomes

Trimethyltin (TMT), in a concentration dependent manner, inhibits in vitro uptake of gamma-aminobutyric acid (GABA), norepinephrine and serotonin by mouse forebrain synaptosomes with IC50S of 75, 43 and 24 microM, respectively. At 2 h and 14 h following in vivo administration of TMT (4.26 mg/kg; i.p.) to mice, GABA and serotonin uptake by forebrain synaptosomes are decreased, although norepinephrine uptake was not significantly affected. In vitro kinetic analyses of TMT inhibition of forebrain synaptosomal uptake of GABA, norepinephrine and serotonin indicated that the inhibition was not of the competitive type. This inhibition of uptake of neurotransmitters could be responsible, at least in part, for altered neurotransmitter levels in the synaptic cleft and may contribute to altered nervous system function during TMT intoxication.