Differential effects of selective and non-selective inhibition of nitric oxide synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer healing.
Nitric oxide synthases (NOS) and cyclooxygenase-2 (COX-2) are important enzymes involved in ulcer healing but interactions between them have not been clearly defined. The aim of this study was to investigate the effects of selective or non-selective inhibition of NOS on the expression and activity of COX-2 during healing of acetic acid-induced gastric ulcers in rats. N-[3-(aminomethyl)benzyl] acetamidine (1400 W), a potent selective inhibitor of inducible nitric oxide synthase (iNOS), at a dose of 0.1 mg/kg/day, was found to reduce the ulcer sizes at day 3 and 7 post-ulcer induction. On the other hand, 15 mg/kg/day of NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor that suppresses both iNOS and endothelial nitric oxide synthase (eNOS), enlarged the ulcer sizes over the same time periods. The expression of COX-2 and COX activity, together with NF-kappaB activation in the ulcer tissues were down-regulated by L-NAME but not 1400 W. It is concluded that iNOS may contribute to ulcer formation while COX-2 and eNOS promote ulcer healing. eNOS enhances COX-2 expression possibly through the activation of NF-kappaB.
Guo
Jin Sheng
JS
Division of Gastroenterology, Department of Internal Medicine, Zhong Shan Hospital, Shanghai Medical College, Fu Dan University, Shanghai, China.
Cho
Chi Hin
CH
Wang
Ji Yao
JY
Koo
Marcel Wing Leung
MW
D019342:Acetic Acid; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D016328:NF-kappa B; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D019342:Acetic Acid; C023731:acetamidine; D019331:NG-Nitroarginine Methyl Ester