The effect of serotonin, its precursors and metabolites on brain glutathione-S-transferase.

Abstract

The isoelectric point and substrate specificity of the main isoform of glutathione-S-transferase (GST, EC 2.5.1.18) isolated from brain stem, hippocampus and parietal cortex of pig brain were determined. The effect of serotonin, its precursors (Try, 5-HTry), physiologically active derivative (melatonin) and final metabolite (5-HIAA) on the activity of this form was examined. Investigation indicated that serotonin did not affect the activity of GST in all studied regions of brain. The inhibitory effect of Try was stronger than that of 5-HTry, but weaker than the one expressed by melatonin and especially by 5-HIAA. Studies on the type of inhibition showed that Try, melatonin and 5-HIAA can compete for the active site with the electrophilic substrate but not with glutathione. Therefore precursors and endogenous derivatives of serotonin but not serotonin itself may affect the detoxification function of brain glutathione-S-transferase and increase the exposure of brain to toxic electrophiles.