Preliminary evidence now exists that glutathione (GSH) acts as a neurotransmitter in the mammalian central nervous systems. Binding constants for receptor sites have been measured using radiolabeled GSH on synaptic membranes and on cultured astrocyte cells. There is evidence for GSH receptor sites in various other CNS structures as well. We propose to synthesize fluorescent GSH probes for the study of these receptor sites and measure their binding constants in competition with radiolabeled GSH. Fluorescence labeled probes with suitable binding constants will be used to study the distribution of binding sites in the CNS and other peripheral tissues and to examine second messenger (IP3) activation in cultured astrocytes. Fluorescent labeling on different GSM functional groups will also help elucidate the nature of the GSM receptor site.
