Glutathione: new candidate neuropeptide in the central nervous system

The physiological significance of glutathione in the mammalian central nervous system is still uncertain, although some evidence indicates that it may be an important regulatory peptide. In the present study, the distribution and characteristics of glutathione binding sites in the brain have been studied. Biotinyl-glutathione was synthesized as a probe to detect glutathione binding sites in the CNS. Specific glutathione binding sites in the brain were largely localized to the white matter, suggesting the presence of glutathione receptors on neuroglial cells. The colloidal gold technique and immunofluorescence double staining allowed the visualization of the receptor at the cellular level and thus demonstrated that there are glutathione receptors on cultured astrocytes. Glutathione applied to cultured astrocytes elicited increased levels of intracellular inositol-1,4,5-trisphosphate, suggesting that glutathione receptors were coupled to phospholipase C. The localization of glutathione receptors on astrocytes and the activation of a second messenger system by glutathione suggest that glutathione may be a neuropeptide in the central nervous system.