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.