Search

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 (AsO3 3−; iAIII), the pentavalent organoarsenic compounds monomethylarsonic acid (CH3AsO(OH)2; MMAV) and dimethylarsinic acid ((CH3)2AsO(OH); DMAV) and the trivalent compounds monomethylarsonous acid (CH3As(OH)2, MMAIII) and dimethylarsinous acid ((CH3)2As(OH); DMAIII) 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 μmol/l and the organic arsenical compounds were tested in concentrations of 0.1–100 μmol/l. We found no significant effects on voltage-operated ion channels; however, the arsenicals exert different effects on glutamate receptors. While MMAV and MMAIII significantly enhanced ion currents through N-methyl- d-aspartate (NMDA) receptor ion channels with threshold concentrations <10 μmol/l, DMAV and DMAIII significantly reduced NMDA-receptor mediated responses with threshold concentrations <0.1 μmol/l; iAIII had no effects on glutamate receptors of the NMDA type. MMAIII and DMAV significantly reduced ion currents through α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor ion channels with threshold concentrations <10 μmol/l (MMAIII) and <1 μmol/l (DMAV). MMAV and iAIII had no significant effects on glutamate receptors of the AMPA type. The effects of MMAV, MMAIII, DMAV and DMAIII on glutamate receptors point to a neurotoxic potential of these substances. [ABSTRACT FROM AUTHOR]