Differential effects of selective and non-selective inhibition of nitric oxide synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer healing

Eur J Pharmacol. 2006 May 1;536(3):301-8. doi: 10.1016/j.ejphar.2005.12.088. Epub 2006 Mar 13.

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