Targeting nitric oxide in the gastrointestinal tract.
This review discusses the contributions of the three nitric oxide (NO) synthase (NOS) isozymes neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) to the function and diseases of the gastrointestinal tract. Small (nanomolar) quantities of NO produced by calcium-dependent nNOS play a physiological role in peristalsis and sphincter function of the intestine. Decreased nNOS function can result in aperistalsis and obstructive sphincters. NO produced by eNOS dilates mucosal blood vessels and prevents leukocyte aggregation, and is therefore essential for the maintenance of mucosal blood flow. Absence of eNOS-derived NO results in an increased susceptibility of the gastrointestinal tract to injury. Selective NO delivery by gene therapy or NO-donating compounds may offer new therapeutic options in motility disorders of the gut and the prevention of mucosal injury. The effects of large (micromolar) amounts of NO as produced by iNOS are less well understood. Large amounts of NO can increase gut permeability, induce apoptosis and stimulate intestinal secretion, while NO can also kill bacteria, block apoptosis and reduce inflammation by inhibiting activation of nuclear factor-kappaB (NFkappaB). Lumenal donation of NO could therefore block NFkappaB activation and be a treatment option in inflammatory conditions of the bowel.
Dijkstra
Gerard
G
Department of Gastroenterology and Hepatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. G.Dijkstra@int.azg.nl
van Goor
Harry
H
Jansen
Peter L M
PL
Moshage
Han
H
D000818:Animals; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III