Diphenyl diselenide and diphenyl ditelluride affect the rat glutamatergic system in vitro and in vivo

The aim of this study was to investigate the possible involvement of the gl utamatergic system in the toxicity of organochalcogens, since this is an im portant neurotransmitter system for signal transduction and neural function . The results indicated that 100 muM diphenyl diselenide (PhSe)(2) and diph enyl ditelluride (PhTe)(2) inhibit by 50 and 70% (P < 0.05), respectively, [H-3]glutamate binding in vitro. Acute administration of 25 <mu>mol/kg (PhS e)(2) or 3 mu mol/kg (PhTe)(2) caused a significant reduction in [H-3]gluta mate (30%, P<0.05) or [H-3]MK-801 binding (30%. P<0.05) to rat synaptic mem branes. These results suggest that (PhSe)(2) and (PhTe)(2) affect, in a rat her complex way, the glutamatergic system after acute in vivo exposure in r ats. In vitro, total [H-3]GMP-PNP binding was inhibited about 40% at 100 mu M (PhSe)(2) and (PhTe)(2). Acute exposure in vivo to (PhSe)(2) decreased th e stable [H-3]GMP-PNP binding to 25% and (PhTe)(2) to 68% of the control va lue (P ( 0.05, for both compounds). Simultaneously, the unstable binding of [H-3]GMP-PNP was decreased about 30 and 50% (P < 0.05, for both compounds) after exposure to (PhSe)(2) and (PhTe)(2), respectively. CMP-PNP stimulate d adenylate cyclase (AC) activity significantly in control animals. (PhSe)( 2)- and (PhTe)(2)-treated animals increased the basal activity of this enzy me, but GMP-PNP stimulation was totally abolished. These results suggest th at the toxic effects of organochalcogens could result from action at differ ent levels of neural signal transduction pathways, possibly involving other neurotransmitters besides the glutamatergic system. (C) 2001 Elsevier Scie nce B.V. All rights reserved.