Medizinische Universität Graz - Research portal
Selected Publication:
Peskar, BM; Maricic, N; Gretzera, B; Schuligoi, R; Schmassmann, A.
Role of cyclooxygenase-2 in gastric mucosal defense.
Life Sci. 2001; 69(25-26):2993-3003
Doi: 10.1016%2FS0024-3205%2801%2901407-2
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- Co-authors Med Uni Graz
- Schuligoi Rufina
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- Abstract:
- Two isoenzymes of cyclooxygenase (COX), the key enzyme in prostaglandin (PG) biosynthesis, COX-1 and COX-2, have been identified. COX-1 was proposed to regulate physiological functions, COX-2 to mediate pathophysiological reactions such as inflammation. In particular, it was suggested that maintenance of gastric mucosal integrity relies exclusively on COX-1. Recently, it was shown that a selective COX-1 inhibitor does not damage the mucosa in the healthy rat stomach, although mucosal prostaglandin formation is near-maximally suppressed. However, concurrent treatment with a COX-1 and a COX-2 inhibitor induces severe gastric damage. This indicates that in normal mucosa both COX-1 and COX-2 have to be inhibited to evoke ulcerogenic effects. In the acid-challenged rat stomach inhibition of COX-1 alone is associated with dose-dependent injury which is aggravated by additional inhibition of COX-2 activity or prevention of acid-induced up-regulation of COX-2 expression by dexamethasone. After acid exposure, COX-2 inhibitors cause substantial gastric injury when nitric oxide formation is suppressed or afferent nerves are defunctionalized. Ischemia-reperfusion of the gastric artery increases levels of COX-2 but not COX-1 mRNA. COX-2 inhibitors or dexamethasone aggravate ischemia-reperfusion-induced mucosal damage up to 4-fold, an effect abolished by concurrent administration of 16,16-dimethyl-PGE2. Furthermore, the protective effects elicited by a mild irritant or intragastric peptone perfusion are antagonized by COX-2 inhibitors. Finally, COX-2 expression is increased in experimental ulcers. COX-2 inhibitors delay the healing of chronic gastric ulcers in experimental animals and decrease epithelial cell proliferation, angiogenesis and maturation of the granulation tissue to the same extent as non-steroidal anti-inflammatory drugs. These observations indicate that, in contrast to the initial concept, COX-2 plays an important role in gastric mucosal defense.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cyclooxygenase 1 -
- Cyclooxygenase 2 -
- Cyclooxygenase 2 Inhibitors -
- Cyclooxygenase Inhibitors - pharmacology
- Dose-Response Relationship, Drug - pharmacology
- Gastric Mucosa - enzymology
- Humans - enzymology
- Indomethacin - pharmacology
- Isoenzymes - physiology
- Membrane Proteins - physiology
- Prostaglandin-Endoperoxide Synthases - physiology
- Rats - physiology
- Stomach Ulcer - chemically induced
- Find related publications in this database (Keywords)
- cyclooxygenase
- COX-1
- COX-2
- gastric mucosal damage
- non-steroidal anti-inflammatory drugs
- ischemia-reperfusion
- ethanol-induced gastric injury
- gastroprotection
- gene expression
- ulcer healing