LOCALIZATION OF A NOVEL PATHWAY FOR THE LIBERATION OF GABA IN THE HUMAN CNS

Serum carnosinase is a dipeptidase, which is synthesized in human brai n, where it hydrolyzes homocarnosine to release free GABA. Immunohisto chemical procedures were used to demonstrate the presence of this enzy me in several layers of the retina and in certain neuronal tracts of t he cerebral cortex, cerebellar cortex, olfactory bulb, hippocampus, an d in disseminated tracts presumably from the internal capsule, intersp ersed among the basal ganglia. The enzyme was also present in the epit helial cells of the choroid plexus and in corpora amylacea, which were seen in many regions of the CNS. Homocarnosine was localized either i n the same tracts or in nearby neurons. For example, the Purkinje cell s of the cerebellar cortex contained homocarnosine, whereas serum carn osinase was localized in adjacent neuronal projections apparently orig inating from outside the cerebellar cortex and having probable synapti c contact with the Purkinje cells. These findings suggest that in addi tion to glutamate decarboxylation, a second metabolic reaction for the formation of free GABA exists in specific neuronal tracts of the huma n CNS where GABA is released from homocarnosine by the action of serum carnosinase.