Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage.
OBJECTIVE
Prostaglandins and nitric oxide are key mediators of gastric mucosal defense. Endotoxemia alters gastric resistance to damage, but little is known of the effects of chronic endotoxemia on the expression of prostaglandin and nitric oxide synthases (NOSs). The effects of short- vs. long-term administration of endotoxin on gastric resistance to damage and on expression of NOS and prostaglandin synthesis were compared.


METHODS
Rats were treated with short- or long-term bacterial endotoxin, after which susceptibility to ethanol-induced damage was assessed. The effects of various inhibitors of prostaglandin and NOS were examined. Expression of gastric NOS and cyclooxygenase (COX) messenger RNA (mRNA) were examined.


RESULTS
Repeated administration of endotoxin increased gastric resistance to ethanol- but not indomethacin-induced injury. Indomethacin, but not a highly selective COX-2 inhibitor or an inducible NOS inhibitor, abolished long-term endotoxin-induced gastric resistance to injury. Expression of mRNA for both COX-1 and -2, but not for endothelial or inducible NOS, were significantly increased after long-term endotoxin administration.


CONCLUSIONS
Repeated exposure to endotoxin resulted in increased resistance of the gastric mucosa to injury through a prostaglandin-dependent pathway. These prostaglandins were produced via COX-1, which like COX-2, is induced by endotoxin administration.
Ferraz
J G
JG
Intestinal Disease Research Unit, University of Calgary, Alberta, Canada.
Sharkey
K A
KA
Reuter
B K
BK
Asfaha
S
S
Tigley
A W
AW
Brown
M L
ML
McKnight
W
W
Wallace
J L
JL
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity; D004731:Endotoxins / Q000009:adverse effects*; D004790:Enzyme Induction; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000201:enzymology* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology*; D007213:Indomethacin / Q000633:toxicity; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D010544:Peroxidases / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D009569:Nitric Oxide; D000431:Ethanol; C044101:endotoxin, Escherichia coli; D010544:Peroxidases; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin