ASPIRIN CAUSES RAPID UP-REGULATION OF CYCLO-OXYGENASE-2 EXPRESSION INTHE STOMACH OF RATS

Background: Cyclo-oxygenase-1 (COX-1) is believed to produce prostagla ndins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is i nduced at sites of inflammation. Little is known about: the regulation of COX-2 in the stomach, particularly during the period following muc osal injury. In this study, we examined COX-1 and COX-2 expression sho rtly after administration of NSAIDs or ethanol. Methods: Fasted rats w ere given aspirin, salicylate, indomethacin or ethanol (20% or 40%) or ally. Three hours later the stomach was excised, the severity of damag e scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immu nohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activ ity were also measured, Results: Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas s alicylate and 20% ethanol caused only superficial epithelial damage. A spirin caused a significant increase in COX-2 mRNA expression and a ma rked increase in COX-2 immunoreactivity, particularly in the superfici al mucosa. Expression of COX-1 (mRNA and protein) was unaffected by as pirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E-2 prevented the induction of COX-2 by aspirin. Sa licylate and indomethacin caused modest increases in COX-2 immunoreact ivity but no change in COX-2 mRNA. Neither concentration of ethanol af fected COX-2 mRNA or protein expression, suggesting that this was a sp ecific response to the aspirin, rather than to injury. Conclusions: Th ese results demonstrate a rapid upregulation of COX-2 expression in re sponse to aspirin, possibly representing a compensatory response to in hibition of gastric prostaglandin synthesis.