Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice

Gastroenterology. 1997 Feb;112(2):387-97. doi: 10.1053/gast.1997.v112.pm9024292.

Abstract

Background & aims: The role of two forms of cyclooxygenase (COX-1 and COX-2) in gastric mucosal lesions is not well understood. The regulation of both forms of COX and the effect of COX-2 on the repair process of gastric mucosal lesions in mice were investigated.

Methods: Gastric mucosal erosions and ulcers were induced experimentally in mice. The level of COX messenger RNA (mRNA) was determined by reverse-transcription polymerase chain reaction. COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist. The effects of long-term administration of NS-398 on gastric ulcers were examined.

Results: COX-2 mRNA levels were not detected in control conditions but were high during the acute stages of gastric erosions and ulcers. COX-2 protein was detected 5 days after ulcer induction but not in control mice. Gastric ulceration was not associated with a change in COX-1 mRNA and protein levels. Administration of NS-398 to mice with ulcers at acute stages impaired the healing of ulcers.

Conclusions: High levels of COX-2 mRNA and protein during the acute stages of gastric mucosal lesions may be involved in the repair process of these lesions in mice.

MeSH terms

  • Acetic Acid
  • Acids
  • Animals
  • Blotting, Western
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Enzyme Induction
  • Ethanol
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Membrane Proteins
  • Mice
  • Nitrobenzenes / pharmacology
  • Polymerase Chain Reaction
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Reference Values
  • Stomach Diseases / chemically induced
  • Stomach Diseases / metabolism*
  • Stomach Diseases / pathology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / metabolism*
  • Stomach Ulcer / pathology
  • Sulfonamides / pharmacology
  • Transcription, Genetic
  • Wound Healing / drug effects

Substances

  • Acids
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Ethanol
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Acetic Acid