Trimethyltin inhibits uptake of neurotransmitters into mouse forebrain synaptosomes

Abstract

Trimethyltin (TMT), in a concentration dependent manner, inhibits in vitro uptake of γ-aminobutyric acid (GABA), norepinephrine and serotonin by mouse forebrain synaptosomes with IC 50 s of 75, 43 and 24 μM, 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 norepinenphrine uptake was not significanlty 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.