N-ACETYLASPARTYLGLUTAMATE CATABOLISM IS ACHIEVED BY AN ENZYME ON THE CELL-SURFACE OF NEURONS AND GLIA

N-Acetylaspartylglutamate (NAAG) is a nervous system-specific, acidic dipeptide which is released from neurons in a manner consistent with a function in synaptic neurotransmission. The hydrolysis of NAAG to pro duce glutamate and N-acetylaspartate was analyzed in cell cultures pre pared from murine brain cells. Peptidase activity against NAAG was fou nd in cultures which contained both neurons and glia, as well as in cu ltures of glia alone. Several lines of evidence were obtained in suppo rt of the hypothesis that this peptidase activity is predominantly bou nd to the extracellular face of the plasma membranes of these cells. G lutamate released from NAAG accumulated in the extracellular medium. E xtracellular application of peptidase inhibitors effectively reduced N AAG hydrolysis. Peptidase activity was not secreted into the cell cult ure medium by intact cells, and lysed cells did not release detectable peptidase activity beyond that obtained with intact cells. Replacemen t of extracellular sodium with choline inhibited peptide uptake while stimulating apparent extracellular NAAG hydrolysis by intact cells in culture. Finally, the steady rise in extracellular glutamate as a cons equence of NAAG hydrolysis by these brain cells, including glia, suppo rts the conclusion that glutamate uptake is not tightly coupled to pep tidase activity and thus that NAAG serves as a significant source of g lutamate in the synaptic space following depolarization-induced peptid e release.