Inhibitors of nitric oxide synthase block carbon monoxide-induced increases in cGMP in retina

Previous studies indicate that the gaseous messengers carbon monoxide (CO) and nitric oxide (NO) can interact to cause robust increases in intracellular cGMP levels in the retina. The purpose of the present study was to investigate the biochemical basis of the interactions between NO and CO for these increases. Turtle retinas were incubated in vitro with CO to stimulate cGMP production in the presence or absence of the nitric oxide synthase inhibitors N-omega-nitro-L-arginine methyl ester and S-methyl-thiocitrulline. Cyclic GMP immunocytochemistry was then used to evaluate the changes in cGMP levels in response to these stimuli. The results indicated that CO itself stimulated increases in cGMP in bipolar and amacrine cells, and that the increases were completely blocked by SMTC and L-NAME. We postulate that the increases of cGMP in response to CO might be mediated, at least partly, by CO displacing and releasing NO from its intracellular storage pool(s).