Arch Toxicol 2006 Aug 01;808:492-501. doi: 10.1007/s00204-006-0074-4.

Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals.

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Pentavalent and trivalent organoarsenic compounds belong to the major metabolites of inorganic arsenicals detected in humans. Recently, the question was raised whether the organic arsenicals represent metabolites of a detoxification process or methylated species with deleterious biological effects. In this study, the effects of trivalent arsenite (AsO(3) (3-); iA(III)), the pentavalent organoarsenic compounds monomethylarsonic acid (CH(3)AsO(OH)(2); MMA(V)) and dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and the trivalent compounds monomethylarsonous acid (CH(3)As(OH)(2), MMA(III)) and dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) were tested on glutamate receptors and on voltage-operated potassium and sodium channels heterologously expressed in Xenopus oocytes. Membrane currents of ion channels were measured by conventional two-electrode voltage-clamp techniques. The effects of arsenite were tested in concentrations of 1-1,000 micromol/l and the organic arsenical compounds were tested in concentrations of 0.1-100 micromol/l. We found no significant effects on voltage-operated ion channels; however, the arsenicals exert different effects on glutamate receptors. While MMA(V) and MMA(III) significantly enhanced ion currents through N-methyl-D: -aspartate (NMDA) receptor ion channels with threshold concentrations <10 micromol/l, DMA(V) and DMA(III) significantly reduced NMDA-receptor mediated responses with threshold concentrations <0.1 micromol/l; iA(III) had no effects on glutamate receptors of the NMDA type. MMA(III) and DMA(V) significantly reduced ion currents through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor ion channels with threshold concentrations <10 micromol/l (MMA(III)) and <1 micromol/l (DMA(V)). MMA(V) and iA(III) had no significant effects on glutamate receptors of the AMPA type. The effects of MMA(V), MMA(III), DMA(V) and DMA(III )on glutamate receptors point to a neurotoxic potential of these substances.

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Species referenced: Xenopus laevis
Genes referenced: mhc2-dma mmd