抄録
Nitric oxide (NO) has been shown to elicit both favorable and unfavourable effects on gastrointestinal (GI) system. NO is generated from L-arginine by two different types of NO synthase (NOS) . One type of NOS, constitutive NOS (cNOS), is con-stitutively expressed by endothelial cells (eNOS) and by neural cells (nNOS) . cNOS-derived NO causes a variety of physiogical effects by stimulating guanylate cyclase-cylic GMP system, effects genereally beneficial to GI system. For example, nNOS-derived NO modulates GI motility. eNOS-derived NO increases mucosal blood flow, and stimulates production of mucus and HCO3-, all of which enhance mucosal defense and repair system. Based on these background, several attemps have been made to use NO as a therapeutic drugs. For example, tetraprenylacetone (teprenone) has been shown to enhance gastric mucosal restitution by upregulating cNOS activity. NO-releasing NSAIDs have been developed to mitigate NSAIDs induced mucosal injury by protection afforded by NO. In contrast, other type of NOS, inducible NOS (iNOS), is transiently expressed in macrophages in response to stimuli, such as bacterial invasion. iNOS generates huge amount of NO, that pre-vents invasion of bacteria, but causes serious injury in host tissues. For example, Helicobacter pylori upregulates iNOS expression in gastric mucosa, and enhances release of NO, thereby accelerating epithelial cell apoptosis. In chronic inflammatory bowel diseases, inceased expression of mucosal iNOS is closely associated with developement of mucosal injury. However, it should be noted that in certain circum-stances iNOS affords mucosal protection against noxious stimuli, and promotes mucosal repair after injury.
