Cyclooxygenase (COX) inhibitors and the intestine.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.
Little
Dianne
D
Colic and Digestive Disease Program, Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA.
Jones
Samuel L
SL
Blikslager
Anthony T
AT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006360:Heat-Shock Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D047495:PPAR gamma; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases