ENDOTOXIN ACTIONS ON MYOELECTRIC ACTIVITY, TRANSIT, AND NEUROPEPTIDESIN THE GUT - ROLE OF NITRIC-OXIDE

The lipopolysaccharide (endotoxin) of gram-negative bacteria has syste mic effects in animals and man. Our aim was to investigate the effects of E. coli lipopolysaccharide on motility and transit through the sma ll intestine in rats and to analyze plasma and tissue concentrations o f intestinal neuropeptides. When lipopolysaccharide (20-160 mu g/kg) w as administered intravenously, the migrating myoelectric complex was r eplaced by spike bursts accompanied by rapid transit. Tissue concentra tions of substance P and neurokinin A decreased, while plasma levels o f calcitonin gene-related peptide increased. N-omega-Nitro-L-arginine, N-omega-L-arginine methyl ester, dexamethasone, or indomethacin preve nted these changes in myoelectric activity and tissue contents of neur opeptides. All of these compounds, except indomethacin, prevented the increased rate of transit. Thus, lipopolysaccharide changes motility t hrough the nitric oxide and arachidonic pathways, resulting in rapid t ransit through the gut.