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

AlCl3, MnCl2, and CdCl2 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 (IC50) of GABA transport were 316 muM, 7.4 mM, and 1.4 mM, respectively. Ca2+ (1 mM) enhanced the inhibitory effect of Al3+ (IC50 decreased to 149 muM) but antagonized that of Mn2+ (IC50 = 10 mM) and Cd2+ (IC50 = 2.1 mM). For glutamate transport 1 mM Ca2+ changed the IC50 values from 299 to 224 micron for Al3+, 7.1 to 10 mM for Mn2+, and 2 to 3 mM for Cd2+. 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 Al3+, Mn2+, and Cd2+ exerted selective and differential effects on the transport systems of neurotransmitter substances in the synaptosomal membrane.