Glutamate carboxypeptidase II is expressed by astrocytes in the adult rat nervous system

The enzyme glutamate carboxypeptidase II (GCP II) has been cloned from rat brain and human prostate. This enzyme, which catabolizes the neuropeptide N -acetylaspartylglutamate, has also been known as N-acetylated alpha-linked acidic dipeptidase (NAALADase), and is identical to the prostate-specific m embrane antigen and to the jejunal folylpoly-gamma-glutamate carboxypeptida se. The goals of the present study were to elucidate the cell specificity a nd regional pattern of GCP II expression in the rat nervous system by using Northern blots and enzymatic assays of brain and subfractionated primary n euronal and glial cultures together with in situ hybridization histochemist ry (ISHH) in sections of adult rat tissue. GCP II activity was assayed in a strocyte cultures (4.4 pmol/mg protein per minute), neuronal-glial cocultur es (2.5 pmol/mg protein per minute) and neuron-enriched cultures (0.38 pmol /mg protein per minute), with the activity in each preparation correlating to its astrocytic content (r = 0.99). No activity was detected in cultured oligodendrocytes or microglia. Northern blots probed with a GCP II cDNA det ected mRNAs exclusively in activity-positive cell preparations. ISHH result s show that GCP II is expressed by virtually all astrocytes, by Bergmann gl ial cells in cerebellum, by Muller cells in retina and by the satellite cel ls in dorsal root ganglia. Astrocytes in select groups of nuclei (e.g., hab enula, supraoptic nucleus, pontine nucleus) contained pronounced levels of GCP II message. The data of the present study suggest that GCP II is expres sed in the adult rat nervous system exclusively in astrocytic glial cells. (C) 1999 Wiley-Liss, Inc.