Role of nitric oxide in inflammation-induced suppression of secretion in a mouse model of acute colitis.
The role of nitric oxide (NO) derived from the inducible isoform of NO synthase (iNOS) in epithelial transport dysfunction was studied in a model of colitis induced in mice by intrarectal 2,4, 6-trinitrobenzenesulfonic acid in 30% ethanol. Expression of iNOS mRNA was determined by RT-PCR. Electrolyte transport studies were conducted in Ussing chambers in which segments of inflamed colon were incubated with or without the selective iNOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL). Seven days after the induction of colitis, colonic tissue exhibited increased myeloperoxidase activity compared with saline controls. There was a detectable basal expression of iNOS mRNA, but expression was increased 3.7-fold in inflamed colons. Inflammation also caused an increase in iNOS activity and a concomitant decrease in constitutive NOS activity. In Ussing chamber experiments, there was a decreased response to electrical field stimulation in inflamed tissue, which was partially reversed by pretreatment of the tissue with L-NIL. The short-circuit current response to the muscarinic agonist carbachol was also reduced in inflammation, but this was not reversed by L-NIL. In summary, NO derived from iNOS mediates, in part, inflammation-induced suppression of neurally evoked electrolyte transport.
MacNaughton
W K
WK
Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Lowe
S S
SS
Cushing
K
K
D000208:Acute Disease; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004573:Electrolytes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D004573:Electrolytes; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D012333:RNA, Messenger; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008239:Lysine