The aim of this study was to investigate the possible involvement of the glutamatergic system in the toxicity of organochalcogens, since this is an important neurotransmitter system for signal transduction and neural function. The results indicated that 100 microM diphenyl diselenide (PhSe)(2) and diphenyl ditelluride (PhTe)(2) inhibit by 50 and 70% (P<0.05), respectively, [(3)H]glutamate binding in vitro. Acute administration of 25 micromol/kg (PhSe)(2) or 3 micromol/kg (PhTe)(2) caused a significant reduction in [(3)H]glutamate (30%, P<0.05) or [(3)H]MK-801 binding (30%, P<0.05) to rat synaptic membranes. These results suggest that (PhSe)(2) and (PhTe)(2) affect, in a rather complex way, the glutamatergic system after acute in vivo exposure in rats. In vitro, total [(3)H]GMP-PNP binding was inhibited about 40% at 100 microM (PhSe)(2) and (PhTe)(2). Acute exposure in vivo to (PhSe)(2) decreased the stable [(3)H]GMP-PNP binding to 25% and (PhTe)(2) to 68% of the control value (P<0.05, for both compounds). Simultaneously, the unstable binding of [(3)H]GMP-PNP was decreased about 30 and 50% (P<0.05, for both compounds) after exposure to (PhSe)(2) and (PhTe)(2), respectively. GMP-PNP stimulated adenylate cyclase (AC) activity significantly in control animals. (PhSe)(2)- and (PhTe)(2)-treated animals increased the basal activity of this enzyme, but GMP-PNP stimulation was totally abolished. These results suggest that the toxic effects of organochalcogens could result from action at different levels of neural signal transduction pathways, possibly involving other neurotransmitters besides the glutamatergic system.