Neuronal nitric oxide synthase expression in neuronal cell differentiation.

Expression of neuronal nitric oxide synthase (n-NOS) was investigated during neuronal cell differentiation. Trace amounts of n-NOS mRNA were detected in the primary culture of neural precursor cell (NPC) at embryonic day 10, and a high level of n-NOS mRNA was observed after a further 7 days cultivation of NPC. Both n-NOS activity and its mRNA level were also increased in the human neuroblastoma cell line, TGW, following trans-retinoic acid (RA)-induced neuronal differentiation. These findings indicate that there is positive regulation of n-NOS mRNA during neuronal cell differentiation. However TGW cell differentiation with trans-RA could not be reversed by treatment with specific inhibitors of NOS. Thus, the signal transduction mechanism which is involved in the induction of neuronal cell differentiation by trans-RA appears to be distinct from the NO-mediated pathway.