Nitric oxide-cyclic GMP-protein kinase pathway

This signaling pathway, mediated by nitric oxide, can protect developing neurons against alcohol toxicity. Nitric oxide (NO) is produced by neuronal nitric oxide synthase (nNOS). Increased levels of NO activate soluble guanylyl cyclase (sGC), which synthesizes cyclic GMP (cGMP). This cyclic nucleotide subsequently activates cyclic GMP-dependent protein kinases (PKG). The kinases phosphorylate downstream targets. One of these downstream targets is the transcription factor, NF-kappa B, which presumably promotes neuronal survival against alcohol by enhancing transcription of neuroprotective genes. Genetic differences in the expression of this pathway can produce marked differences in vulnerability to alcohol teratogenesis in mice and may underlie differences in outcome among humans exposed to alcohol in utero. (Contributed by Dr. Daniel Bonthius.)