The effects of homocysteine and homocysteic acid on the metabotropic glutamate receptors of cerebellar neurons

Incubation of cerebellar neurons with homocysteine or homocysteic acid at a concentration of 500 μM for 30 min increases the intracellular level of free radicals. Specific antagonists of metabotropic glutamate receptors of the groups I (AIDA) and III (MSOP) decreased the accumulation of reactive oxygen species in cells, which suggests that homocysteine and homocysteic acid can interact with these receptors. Inhibition of NO-synthase does not affect the level of free radicals, which indicates that NO• did not contribute to an increase in the level of free radicals in neurons under our conditions. Neither homocysteine nor homocysteic acid induced neuronal death; however, both compounds inhibited neuronal Na/K-ATPase. Inhibition of Na/K-ATPase was stronger in the case of activation of ionotropic glutamate receptors by NMDA as compared to simultaneous activation of both ionotropic and metabotropic glutamate receptors by homocysteine or homocysteic acid.