Aspirin causes rapid up-regulation of cyclo-oxygenase-2 expression in the stomach of rats

Aliment Pharmacol Ther. 1997 Dec;11(6):1101-8. doi: 10.1046/j.1365-2036.1997.00247.x.


Background: Cyclo-oxygenase-1 (COX-1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is induced at sites of inflammation. Little is known about the regulation of COX-2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX-1 and COX-2 expression shortly after administration of NSAIDs or ethanol.

Methods: Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.

Results: Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX-2 mRNA expression and a marked increase in COX-2 immunoreactivity, particularly in the superficial mucosa. Expression of COX-1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E2 prevented the induction of COX-2 by aspirin. Salicylate and indomethacin caused modest increases in COX-2 immunoreactivity but no change in COX-2 mRNA. Neither concentration of ethanol affected COX-2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.

Conclusions: These results demonstrate a rapid up-regulation of COX-2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / therapeutic use*
  • Cyclooxygenase 2
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / enzymology
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Male
  • Nitric Oxide Synthase / genetics
  • Peroxidases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Time Factors
  • Up-Regulation


  • Isoenzymes
  • RNA, Messenger
  • Peroxidases
  • Nitric Oxide Synthase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin