[Multiple roles of inducible cyclooxygenase-2 and its selective inhibitors].
Cyclooxygenase (COX) is the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin endoperoxides. In addition to constitutive COX-1, inducible COX-2 has been discovered. COX-2 is induced not only in acute exudative rat carrageenin-induced pleurisy, but in granuloma formation/proliferative inflammation for the acceleration of angiogenesis. This means that COX-2 is induced in the healing process of wounds such as in granuloma of gastric ulcer and the proliferative stage of endometrium. COX-2 is also introduced in ovulation and parturition. Osteoblasts induce COX-2 to accelerate bone absorption. Induction of COX-2 in colon carcinoma is a recent, very exciting topic of investigation. We can learn about many unknown roles of COX-2 from its knockout mouse, but the results must be interpreted cautiously. Development of selective COX-2 inhibitors, such as NS-398, opened a new era in which the side effects of gastric and renal lesions by NSAIDs could be ignored. However, prolongation of would healing by the inhibitors and transient expression of COX-2 must be considered in medical intervention with selective COX-2 inhibitors. Nevertheless, acute exudative inflammation, granuloma formation and bone absorption in rheumatoid arthritis are good targets for these inhibitors and application of these inhibitors will be extended to dysmenorrhea, interruption of abortion and increasing survival rate of patients with colon carcinoma.
Katori
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases