Nitric oxide (NO.) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro.

Recent observations suggest that nitric oxide (NO(.)) can increase or decrease growth cone motility. Here, these apparently paradoxical results are explained by distinct actions of different NO-related species. Filopodial morphology of 223 rat retinal ganglion cells was monitored under computer-enhanced video microscopy in the presence of NO synthase (NOS) substrates or inhibitors, donors of specific NO-related species, and membrane-permeant cyclic nucleotide analogs. Physiological NOS activity induced filopodial outgrowth, whereas inhibition of NOS stabilized filopodia. Similar to NOS, nitrosonium (NO(+) transfer) and peroxynitrite (ONOO(-)), which can regulate the activity of growth-associated proteins by S-nitrosylation and oxidation, respectively, induced filopodial outgrowth. In contrast, NO(.), which stimulates guanylate cyclase to increase cGMP, stabilized filopodial activity. Thus disparate NO-related species may offer a dynamic process of filopodial growth regulation.