Endotoxin actions on myoelectric activity, transit, and neuropeptides in the gut. Role of nitric oxide.
The lipopolysaccharide (endotoxin) of gram-negative bacteria has systemic effects in animals and man. Our aim was to investigate the effects of E. coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyze plasma and tissue concentrations of intestinal neuropeptides. When lipopolysaccharide (20-160 micrograms/kg) was administered intravenously, the migrating myoelectric complex was replaced by spike bursts accompanied by rapid transit. Tissue concentrations of substance P and neurokinin A decreased, while plasma levels of calcitonin gene-related peptide increased N omega-Nitro-L-arginine, N omega-L-arginine methyl ester, dexamethasone, or indomethacin prevented these changes in myoelectric activity and tissue contents of neuropeptides. All of these compounds, except indomethacin, prevented the increased rate of transit. Thus, lipopolysaccharide changes motility through the nitric oxide and arachidonic pathways, resulting in rapid transit through the gut.
Hellström
P M
PM
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
al-Saffar
A
A
Ljung
T
T
Theodorsson
E
E
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015288:Neurokinin A / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism
D008070:Lipopolysaccharides; D009479:Neuropeptides; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D003907:Dexamethasone; D015288:Neurokinin A; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester