Regulation of cyclooxygenase enzymes by nitric oxide.
Nitric oxide (NO), derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS) is involved in the regulation of several important physiological and pathophysiological functions. The mechanisms by which NO exerts some of its beneficial or detrimental effects include activation of guanylate cyclase, formation of peroxynitrite, apoptosis, and regulation of cyclooxygenase (COX). Cyclooxygenase (COX) is the enzyme that converts arachidonic acid to prostaglandins (PG), prostacyclin (PGI2) and thromboxane A2. The role of NO in the regulation of COX and its importance in physiology, pathology and therapy will be reviewed. Evidence will be presented to suggest that COX enzymes are targets for the physiopathological roles of NO and that once activated in the presence of NO, they represent important transduction mechanisms for its multifaceted actions.
Salvemini
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Discovery Pharmacology, G.D. Searle Co., St. Louis, Missouri 63167, USA.
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D010974:Platelet Aggregation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D015398:Signal Transduction; D013927:Thrombosis / Q000188:drug therapy; D014664:Vasodilation
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases