Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications.
The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity explains both therapeutic and side effects of non-steroidal anti-inflammatory drugs (NSAIDs). Indeed, new pharmacological results suggest that COX-2 inhibition provides the therapeutic (ie, anti-inflammatory) activity of NSAIDs, whereas inhibition of constitutive COX-1 is responsible for their gastric and renal side effects as well as for their antithrombotic activity. However, a role of COX-1 in inflammation cannot be excluded. Furthermore, the functional relevance of COX-2 expression and induction in various tissues warrants further investigation. These studies should help in predicting potential adverse effects as well as new indications for selective COX-2 inhibitors.
Department of Biological Research, Boehringer Ingelheim Research Laboratories, Biberach an der Riss, Germany.
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Pairet
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Engelhardt
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases