Selective inhibition of L-glutamate and gammaaminobutyrate transport in nerve ending particles by aluminium, manganese, and cadmium chloride

AlCl 3, MnCl 2, and CdCl 2 inhibited the rates of accumulation of 14C] L-glutamate and 3H] gammaaminobutyrate (GABA) in purified rat forebrain nerve-ending particles in a dose-dependent fashion. The concentrations that would give 50% inhibition (IC 50) of GABA transport were 316 μM, 7.4 mM, and 1.4 mM, respectively. Ca 2+ (1 mM) enhanced the inhibitory effect of Al 3+ (IC 50 decreased to 149 μM) but antagonized that of Mn 2+ (IC 50 = 10 mM) and Cd 2+ (IC 50 = 2.1 mM). For glutamate transport 1 mM Ca 2+ changed the IC 50 values from 299 to 224 μm for Al 3+, 7.1 to 10 mM for Mn 2+, and 2 to 3 mM for Cd 2+. In contrast, the rates of accumulation of 14C] 2-deoxy-glucose and 3H] L-phenylalanine were mostly unaffected by these metal ions. The results indicate that Al 3+, Mn 2+, and Cd 2+ exerted selective and differential effects on the transport systems of neurotransmitter substances in the synaptosomal membrane.