Displacement of [ 3H]glutathione by cysteine and glutathione derivatives in pig cerebral cortical synaptic membranes

Abstract

The pharmacology and structure-function relationships of the binding of glutathione (y-glutamylcysteinylglycine, GSI-I) to its specific receptors in the central nervous system have not been characterised. We have tested the effects of cysteine analogues, y-glutamyl dipeptides and glutathione derivatives on the Nd-independent binding of [3H]GSH to pig cortical synaptic membranes. GSH, oxidized glutathione (GSSG), S-nitrosoglutathione, y-Lglutamylcysteine, cyste-inylglycine, cysteine and cystamine were the most potent displacers (IC50 values in the micromolar range), ghttathione sulfonate and the Salkyl derivatives of glutathione (S-methyl-, -ethyl-, propyl-, -butyl-, penthylglutathione), Lhomocysteate and aminomethanesulfonate exhibited moderate efficacy, some y-glutamyl dipeptides were very weak displacers and Lcysteate, taurine and homotaurine inactive. At 1 mM y-Lglutamylleucine, y-L-glutamyl-GABA and y-Dglutamyltaurine slightly activated the binding. We conclude that the cysteinyl moiety and the free thiol group of glutathione is crucial in the binding.