Fig. 10.

Schematic diagram demonstrating the effects of proinflammatory cytokines on pathways that regulate cGMP levels in colonic longitudinal smooth muscle cells. In longitudinal smooth muscle, cGMP levels are regulated by the activities of sGC and PDE5; the activity of the latter is stimulated via PKG-mediated phosphorylation. Proinflammatory cytokines inhibited sGC activity via iNOS-mediated S-nitrosylation, induced PDE1A expression via NF-κB, and stimulated cGMP hydrolysis, leading to suppression of cGMP formation and a decrease in muscle relaxation.