NITRIC-OXIDE LIMITS TRANSCRIPTIONAL INDUCTION OF NITRIC-OXIDE SYNTHASE IN CNS GLIAL-CELLS

Nitric oxide (NO) can modulate directly and indirectly the activity of a variety of enzymes, including nitric oxide synthase (NOS). In addition, it appears that the NO formed by astroglial cells in which transcriptional induction of NOS has been evoked by cytokines affects NOS mRNA level. We have observed that induction in the presence of NOS inhibitors or NO-trapping agents amplifies NOS mRNA expression and that this effect is reversed by an NO donor. Rather than promoting mRNA instability, NO appears to inhibit the transcriptional induction of NOS. This effect of NO on induction of the NOS gene provides a mechanism by which the temporal and perhaps spatial production in the nervous system of NO, a reactive and potentially toxic mediator, can be finely regulated. (C) 1994 Academic Press, Inc.