Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetic Acid
-
Amidines / pharmacology
-
Animals
-
Benzylamines / pharmacology
-
Blotting, Western
-
Cyclooxygenase 2 / genetics*
-
Cyclooxygenase 2 / metabolism
-
Enzyme Inhibitors / pharmacology*
-
Gastric Mucosa / metabolism
-
Gene Expression Regulation, Enzymologic / drug effects
-
Male
-
NF-kappa B / metabolism
-
NG-Nitroarginine Methyl Ester / pharmacology
-
Nitric Oxide Synthase / antagonists & inhibitors*
-
Nitric Oxide Synthase / metabolism
-
Nitric Oxide Synthase Type II / antagonists & inhibitors
-
Nitric Oxide Synthase Type II / metabolism
-
Nitric Oxide Synthase Type III / antagonists & inhibitors
-
Nitric Oxide Synthase Type III / metabolism
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Rats, Sprague-Dawley
-
Reverse Transcriptase Polymerase Chain Reaction
-
Stomach / drug effects*
-
Stomach / pathology
-
Stomach Ulcer / chemically induced
-
Stomach Ulcer / metabolism
-
Stomach Ulcer / prevention & control*
-
Time Factors
-
Wound Healing / drug effects
Substances
-
Amidines
-
Benzylamines
-
Enzyme Inhibitors
-
N-(3-(aminomethyl)benzyl)acetamidine
-
NF-kappa B
-
RNA, Messenger
-
Nitric Oxide Synthase
-
Nitric Oxide Synthase Type II
-
Nitric Oxide Synthase Type III
-
Cyclooxygenase 2
-
Acetic Acid
-
acetamidine
-
NG-Nitroarginine Methyl Ester