Modulation of glutamate receptor functions by glutathione

In addition to its well-known antioxidant effects, glutathione apparently h as an additional double role in the central nervous system as a neurotransm itter and neuromodulator. A number of recent neurochemical, neuropharmacolo gical and electrophysiological studies have yielded evidence on both functi ons. As an excitatory neurotransmitter, glutathione depolarizes neurons by acting as ionotropic receptors of its own which are different from any othe r excitatory amino acid receptors. As a neuromodulator, it displaces ionotr opic glutamate receptor ligands from their binding sites and regulates calc ium influx through N-methyl-D-asyartate receptor-governed ionophores. In br ain slices glutathione has been shown to regulate the release of other tran smitters, e.g., gamma-aminobutyrate and dopamine, mediated by N-methyl-D-as partate receptors. In the present article, we review recent findings on the neuromodulatory actions of glutathione and discuss possible physiological and pathophysiological consequences. (C) 2000 Elsevier Science Ltd. All rig hts reserved.