REGULATION OF NEUROPEPTIDE-PROCESSING ENZYMES BY NITRIC-OXIDE IN CULTURED ASTROCYTES

Nitric oxide (NO), a recently discovered neurotransmitter, has been sh own to have a cytostatic effect on cultured glia. A NO-generating agen t, S-nitroso-N-acetyl-penicillamine (SNAP), was used to treat C6 gliom a and primary cortical astrocytes. The levels of a monobasic peptide-p rocessing enzyme activity and carboxypeptidase E activity were examine d. The cellular levels of these two enzymes are specifically reduced i n response to treatment with SNAP. A decrease of similar to 30-50% in these two enzyme activities was seen in both primary astrocytes and C6 glioma cells. This decrease in cellular enzyme activities is not due to increased secretion because the secreted activity is also reduced i n response to SNAP treatment in both the glioma cells and the primary astrocytes. Removal of SNAP treatment causes the carboxypeptidase enzy me activity to return to control levels within 3 days. Northern and we stern blot analyses indicate that the reduced cellular level of carbox ypeptidase E is not due to reduced expression of the messenger RNA or protein, suggesting that the SNAP treatment is affecting factors that influence carboxypeptidase E activity. Taken together, these results i mply that NO is involved in the regulation of peptide biosynthetic enz ymes and this could lead to the antimitogenic action of SNAP on glia.